1 Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109; and 2 Department of Pharmacology, George Washington University, Washington, District of Columbia 20037
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To understand vago-vagal reflexes, one must have an appreciation of the events surrounding the encoding, integration, and central transfer of peripheral sensations by vagal afferent neurons. A large body of work has shown that vagal afferent neurons have nonuniform properties and that distinct subpopulations of neurons exist within the nodose ganglia. These sensory neurons display a considerable degree of plasticity; electrophysiological, pharmacological, and neurochemical properties have all been shown to alter after peripheral tissue injury. The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neuronal neighbors. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target.
vagus; visceral afferents
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
TO FULLY UNDERSTAND VAGO-VAGAL reflexes, one must appreciate all aspects of the reflex response from transduction of the sensory signal by receptors on vagal afferent nerve terminals to the transfer and integration of this peripheral signal centrally to the efferent vagal output and resultant response in the target organ. The initiation of vago-vagal reflexes, the receptors transducing the signals, and the mechanisms involved in their transduction by vagal afferent terminals has been dealt with in the previous article in this themes series by Powley and Philips (37a) and the events surrounding the central integration and efferent vagal response will be dealt with subsequently. This review will concentrate on the sensory component of vago-vagal reflexes at the level of the vagal afferent neurons in the nodose ganglion.
It has been known for quite some time that the esophageal distension produced by swallowing elicits a powerful reflex relaxation of the proximal stomach, which increases gastric volume and decreases intragastric pressure to allow efficient transfer of swallowed food into the stomach (7). Investigations by several laboratories have demonstrated that this gastroinhibition is dependent on an intact vagal nervous system (39). Further studies have revealed that stimulation of vagal afferents at different levels of the gastrointestinal tract elicits other vagally mediated gastrointestinal reflexes, including inhibition of food intake (45), inhibition of gastric emptying (40), motility (23), acid secretion (30), and pancreatic secretion (27). Vago-vagal reflexes are not, however, restricted to the gastrointestinal system. For example, activation of cardiac vagal afferent neurons elicits the Bezold-Jarish reflex comprised of an increase in cardioinhibitory parasympathetic activity and a decrease in sympathetic activity resulting in bradycardia and hypotension (4). Similarly, activation of respiratory vagal afferents evokes bronchoconstrictions (26).
![]() |
ORGANIZATION OF VAGAL AFFERENT (SENSORY) NEURONS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The cell bodies of gastrointestinal, respiratory, and cardiac vagal afferent neurons are contained within the nodose and jugular ganglia. The central fibers of these bipolar neurons continue to ascend in the vagus nerve, they enter the brain stem through the solitary tract, and finally synapse on neurons in the nucleus of the nucleus of the solitary tract (NTS) in the medulla. Anatomical, chemical, and physiological studies have shown that at the level of the brain stem, gastrointestinal vagal afferent terminal fields have discrete localizations within the NTS (1, 31). Similarly, retrograde tracing studies have shown that gastrointestinal vagal parasympathetic motor neurons are organized in a viscerotopic mediolateral columnar arrangement that spans the entire rostrocaudal extent of the rat dorsal motor nucleus of the vagus (14). With such an advanced level of organization of vagal afferent nerve terminals, vagal efferent neurons, and vagal efferent nerves, it is reasonable to expect that vagal afferent neurons themselves would also exhibit some degree of organization. Indeed, within the nodose ganglion, neurons tend to be organized in a viscerotopic manner. Neurons that innervate the esophagus or the intestine are located rostrally, whereas neurons that innervate the stomach and pancreas are located more caudally; neurons that innervate the aortic depressor nerve are located rostrally within the nodose ganglion (46).
![]() |
ELECTROPHYSIOLOGICAL PROPERTIES OF VAGAL AFFERENT NEURONS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
A large body of work has been written about the electrophysiological properties of nodose ganglion neurons. From studies using extracellular recording techniques, it is known that vagal afferent neurons have a low level of spontaneous activity and that their action potential firing rate increases upon stimulation of the afferent terminal field. For example, intestinal vagal afferent neurons are excited by a variety of mechanical and chemical stimuli such as gastric or intestinal distension or in response to osmotic stimuli or perfusion of carbohydrates or lipids (18). Intracellular and whole cell patch-clamp recordings made from dissociated neurons revealed the nonuniform nature of vagal afferent neuronal active and passive properties (32, 44). Indeed, intracellular recordings from intact nodose ganglia indicated that some level of organization may exist with regard to electrophysiological properties, because neurons with particular attributes were found to have discrete localizations within the ganglion. In the guinea pig nodose ganglion, for example, a small subpopulation of neurons restricted to the midcaudal pole displays a slow afterhyperpolarization after action potential firing (44).
Unfortunately, the very nature of these blind recording techniques does not allow a distinction to be made among gastrointestinal, respiratory, and cardiovascular vagal afferent neurons within the nodose ganglion. By consequence, it has not been possible to state with absolute conviction what, if any, degree of functional specialization exists. That is to say it has not been possible to determine whether the observed differences in neuronal properties were related to the peripheral target organ of innervation or their sensory function, i.e., mechano-, osmo-, or chemosensitive.
Significant advances, however, have been made recently by combining electrophysiological recording techniques with neuronal tracing methods. The combination of these techniques has made it possible to record from dissociated vagal afferent neurons identified as per their target organ of innervation. In the rat, for example, we have shown that ~80% of gastrointestinal vagal afferent neurons display phasic or rapidly adapting action potential firing properties, with the remaining 20% of neurons displaying tonic, or slowly adapting, action potential firing properties (6). Approximately 45% of gastrointestinal vagal afferent neurons display the hyperpolarization-activated nonspecific cation current IH, whereas only 17% display the fast transient outward voltage-dependent potassium current, IA. The importance of the presence of these currents stems from their capability to determine the behavior of the neuronal membrane. In fact, the IH current has previously been identified in several neuronal systems as contributing to pacemaker activity (43) and in nodose neurons, has been shown to be an important target for modulation by neurotransmitters (25). The IA current acts to increase interspike interval and grade the rate of action potential firing (10). The presence of these currents in subpopulations of gastrointestinal neurons suggests that action potential firing rates may be modulated differently by various stimuli impinging on nodose neurons, either by neurotransmitters or neuromodulators or by frequency-dependent coding of vagal afferent receptor transduction.
Although relatively little is known about the properties of
gastrointestinal vagal afferent neurons, far more information is
available regarding the properties of cardiac and respiratory vagal
afferent neurons. Baroreceptor neurons are by definition mechanosensitive neurons, yet recent work has only just started to
identify the channels and mechanisms responsible for stretch sensitivity. Exposure to hypoosmotic solution increases the conductance in the cell bodies of aortic baroreceptor neurons (identified by a
fluorescent tracer applied to the aortic arch) as well as in some, but
not all, additional neurons from the nodose ganglia (11).
This whole cell current has a reversal potential of approximately 11
mV and can be blocked by the mechanosensitive channel blocker gadolinium (11).
However, this gadolinium-sensitive current has some characteristics that do not correlate well with baroreceptor function, such as the long delay between stimulus and activation. For example, in vivo, the aortic arch multifiber baroreceptor activity responds dramatically within milliseconds to changes in pressure or stretch in the aortic arch (2). At the soma, the response to mechanical stimulation reaches its peak only after 2 s and the response to a single mechanical deformation persists for 30 s (12). However, in response to a hypoosmotic stimulus, the change in conductance at the soma of aortic baroreceptors does not occur immediately, but first occurs at 3 min after the stimulus, and the peak response occurs after 5-7 min (11). Other work also questions whether the gadolinium-sensitive currents at the soma are representative of the mechanosensitive mechanisms at the sensory endings. Although both the mechanically and osmotic stimulated current at the soma can be blocked by gadolinium when applied to the baroreceptor sensory endings, gadolinium has produced conflicting results. In one study (19), carotid sinus baroreceptor activation was reduced by gadolinium, whereas in another study (2), gadolinium had no direct effect on aortic baroreceptor mechanotransduction.
In more recent work, DEG/ENaC proteins have been implicated in mechanotransduction. Subunits of these proteins have been localized to the baroreceptor sensory endings and the cell bodies of baroreceptor neurons in the nodose ganglia (13). Amiloride, which blocks ENaC channels, inhibited the increases in intracellular calcium in the soma of cultured baroreceptor neurons in response to mechanical stimulation (13). Application of benzamil, an amiloride analog, to the carotid sinus blocked the pressure-evoked increase in baroreceptor activity and blunted the reflex responses (13). However, the specificity of both amiloride and benzamil is uncertain, because these drugs also inhibit other electrically active mechanisms such as Na+/H+ and Na+/Ca2+ exchangers.
![]() |
PHARMACOLOGY OF VAGAL AFFERENT NEURONS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Despite being asynaptic (28), vagal afferent neurons have been shown to respond to a variety of neurotransmitters/neuromodulators (25, 33, 42, 44). The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neighbors (36) (see DOES MODULATION OF IONIC CHANNELS IN NODOSE CELL BODY CORRELATE WITH TRANSMITTER RELEASE CENTRALLY?). Therefore, with the exception of a few studies in which the peripheral target of innervation was identified without doubt before electrophysiological recordings by the use of retrograde tracer application to the peripheral target organ (5, 6, 16, 32), the overall problem still remains that one cannot be certain from what type of neuron (gastrointestinal, cardiac, or respiratory) one is recording.
Our recent studies have shown that striking regional differences exist
with respect to some pharmacological properties of identified
gastrointestinal vagal afferent neurons. For example, although the
proportion of gastrointestinal neurons that respond to substance P with
a membrane depolarization (~20%) is independent of the region of
innervation, the proportion of neurons that respond to serotonin
[5-hydroxytryptamine (5-HT)] with a membrane depolarization is very
much dependent on the region of innervation. Although the majority of
neurons innervating the corpus or the duodenum (71 and 78%,
respectively) respond to 5-HT, very few neurons innervating the fundus
(31%), or especially the antrum/pylorus (14%), do so (6). These results support the observation that 5-HT
released from enterochromaffin cells in the duodenum might be
the principal sensory neurotransmitter relaying gastrointestinal
information centrally. On the other hand, it seems quite unlikely that
sensory transduction from the proximal stomach or the antrum/pylorus
region will be relayed via 5-HT. Furthermore, regional differences also exist with respect to the type of response to 5-HT. We have observed three types of response to 5-HT in gastrointestinal vagal afferent neurons: 1) a fast transient 5-HT3-mediated
response; 2) a slower, more maintained
5-HT2-mediated response; and 3) a mixed response with both fast (5-HT3) and slow (5-HT2)
components (Fig. 1). Although the slow
5-HT2-mediated response was observed only rarely in nodose neurons innervating the intestine (<10%), it composed almost 50% of
the responses observed in neurons innervating the stomach
(6).
|
Thus it would appear that the 5-HT-mediated responses of
gastrointestinal vagal afferent neurons show regional-dependent
variations in both the frequency of responding neurons as well as in
the receptor subtypes involved. Responses of nodose neurons to 5-HT appear to be open to modulation. In guinea pig airway-sensitive vagal
afferent neurons, for example, a line of research has demonstrated that
vagal afferent neurons can be sensitized to nociceptive
neurotransmitters such as neurokinins. Although naive airway-sensitive
neurons are insensitive initially to neurokinins, after exposure to
inflammatory antigens such as serotonin, histamine, bradykinin, or
prostaglandins, subsequent reapplication of neurokinin induces a
membrane depolarization, i.e., exposure to inflammatory mediators
uncovers previously silent receptors, and this period of sensitization
can last for periods from hours to days (34, 44). Our
recent studies in identified rat gastrointestinal neurons have shown
that previously silent neurokinin receptors can be uncovered in
response to application of serotonin in a small proportion of neurons.
Unlike guinea pig airway-sensitive neurons, where this sensitizing
action of 5-HT has been shown to involve activation of
5-HT3 receptors (33), the unmasking of
neurokinin receptors on gastrointestinal vagal afferent neurons appears
to involve activation of 5-HT2 receptors (Fig.
2). Given the apparent regional
specialization with regard to serotonin receptor distribution, i.e.,
the predominance of 5-HT2-mediated responses in gastric
rather than intestinal neurons, this may indicate a more prominent role
of sensitization in gastric neurons.
|
Another example of the plasticity of nodose neuronal properties is illustrated with the recent finding that after the induction of experimental gastric ulcers, vagal afferent neurons become more excitable (16). With the use of injections of acetic acid into the stomach wall as a means of inducing gastric ulcers, it has been shown that in nodose neurons identified as projecting to the stomach, there are significant changes in the characteristics of voltage-sensitive sodium currents. In fact, after induction of gastric ulcers, the TTX-resistant sodium current is enhanced, whereas the TTX-sensitive sodium current remains inactive for a shorter period of time than in control. The consequence of these alterations in sodium currents is that gastric nodose neurons become more excitable (16).
The neurochemical phenotype of vagal afferent neurons is also subject
to alteration after tissue insult. Although it is known that allergic
inflammation of guinea pig airways increases the levels of sensory
neuropeptides in nodose neurons (8), a recent study
demonstrated with electrophysiological and immunohistochemical techniques that after inflammation, there is a profound alteration in
the neurochemical coding of vagal afferent neurons. Specifically, after
inflammation, mechanosensitive, low-threshold A fibers express
substance P or calcitonin gene related polypeptide that may be
released centrally from vagal afferents (35). This
alteration in the neurochemical phenotype of mechanosensitive neural
elements would imply that simple mechanical deformations, which are
nonnoxious in the normal state, would potentially result in the release
of neuropeptides traditionally associated with noxious stimuli,
inducing a potential hypersensitivity to deformation after inflammation.
![]() |
DOES MODULATION OF IONIC CHANNELS IN NODOSE CELL BODY CORRELATE WITH TRANSMITTER RELEASE CENTRALLY? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
One important question to be addressed regarding vagal afferent
sensory neurons is, do the ionic channels and their modulation in the
nodose cell body correlate with transmitter release from these neurons
in the NTS? Calcium influx through voltage-gated calcium currents is
necessary for the release of neurotransmitters from synaptic endings,
but it cannot be assumed that the calcium currents at the soma
represent those involved in transmitter release. In many neurons, the
pharmacological profile of calcium currents at the soma does not match
the channels responsible for transmitter release (22, 37).
The types of voltage-gated calcium currents at the soma of identified
aortic baroreceptors have been characterized and are comprised of a
small T-type current. Larger, high-threshold calcium currents that are
comprised mostly of N-type currents with a small P-type component are
also present (32). To determine the calcium
channels responsible for transmitter release at their synaptic endings,
the nerve fibers of these neurons were stimulated in the solitary tract
to evoke postsynaptic responses in NTS neurons that receive these
monosynaptic inputs. The N-type calcium channel antagonist
(-conotoxin-GVIA) blocked most of the excitatory synaptic neurotransmission to NTS neurons, whereas a smaller component was
sensitive to the P-type antagonist agatoxin-IVA (32).
Therefore, in aortic baroreceptor neurons, the calcium currents
at the soma highly correspond to the calcium channels responsible for
transmitter release at their synaptic terminals in the NTS
(32).
It therefore seems reasonable to extrapolate that modulation of
voltage-gated calcium currents at the soma of aortic baroreceptors would predict modulation of neurotransmission from baroreceptors to NTS
neurons at the first synapse of the baroreflex pathway. Recent work
with both opioid and metabotropic glutamate receptor agonists support
this conclusion. µ-Opioid agonists inhibit voltage-gated calcium
currents in the soma of baroreceptor neurons (20).
Consistent with this inhibition at the soma, µ-opioid agonists
depress glutamate-mediated excitatory postsynaptic potentials in NTS
neurons evoked by stimulation of the solitary tract (38).
Activation of metabotropic glutamate receptors has been shown to
suppress voltage-gated calcium currents and, in particular, the
-conotoxin-GVIA-sensitive N-type voltage-gated calcium currents in
nodose neurons (21). Consistent with this inhibition at
the soma, activation of metabotropic glutamate receptors inhibited the
excitatory postsynaptic responses in NTS neurons evoked upon
stimulation, and this inhibition was mediated, in part, by
-conotoxin-GVIA-sensitive N-type calcium currents (17). Recent work has confirmed and extended these results by determining that groups II and III, but not group I, metabotropic glutamate agonists inhibit the activation of NTS neurons evoked upon stimulation of the solitary tract (9).
![]() |
DOES MODULATION OF IONIC CURRENTS AT CELL BODY ALTER AFFERENT ACTIVITY? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although there are no synaptic contacts in the nodose ganglia,
vagal afferent neurons have been shown to respond to a variety of
neurotransmitters/neuromodulators (3, 25, 33, 42, 44).
Despite being asynaptic, a recent report (36) has
demonstrated that stimulation of a subpopulation of nodose neurons can
enhance the activity of its unstimulated neighbors. Part of this
cross-activation may be due to a diffusible messenger or transmitter
release, because it can be blocked by the nonselective calcium channel
antagonist cadmium and evokes a decrease in membrane resistance and
current that reverses at approximately 25 mV (36). In
other nodose neurons, however, an excitation occurred that was not
associated with a resistance change and could have been due to
activity-dependent changes in extracellular potassium concentrations
(36). Potential diffusible mediators of the
cross-excitation include serotonin. Serotonin is released from cell
bodies in the nodose ganglia, and this release is calcium dependent but
not inhibited by blocking TTX-sensitive sodium channels
(15). Serotonin has been shown to depolarize nodose
neurons (6, 33), but in other work, it has been shown to
inhibit the excitation caused by hypoosmotic mechanical stress
(29). The ability of nodose neurons to influence the
activity of unstimulated neighbors may be a mechanism behind some
examples of pathological disturbances in one organ affecting another
organ. It is well known, for example, that a clear relationship exists
between patients with airway hyperresponsiveness and gastroesophageal reflux disease (24), or irritable or inflammatory bowel
disease (41). The ability of nodose neurons to communicate
with each other may suggest that some of these effects may occur at the level of the vagal afferent neurons themselves.
In summary, clearly, vagal afferent neurons have nonuniform properties, and there is enough evidence emerging to state with a reasonable degree of confidence that the electrophysiological properties of vagal afferent neurons are specialized to their sensory function and/or target organ of innervation. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target. Recent studies of the neurobiology of nodose neurons has helped advance our understanding of three major functions of these neurons: sensory transduction, modulation of their activity at the soma, and synaptic neurotransmission from their synaptic endings in the medulla. However, further work is clearly needed to 1) correlate mechanosensitive channels identified at the soma with sensory transduction at the sensory endings; 2) identify paracrine messengers that are released and modulate ionic currents and activity at the soma; and 3) characterize the modulation of calcium channels that regulate transmitter release at the synaptic endings in these visceral afferent neurons.
![]() |
ACKNOWLEDGEMENTS |
---|
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-34944-17 (to Michigan Gastrointestinal Peptide Research Center) and DK-55530 and by National Heart, Lung, and Blood Institute Grants HL-59895 and HL-49965.
![]() |
FOOTNOTES |
---|
Due to space limitations, the authors were unable to provide an exhaustive reference list.
Address for reprint requests and other correspondence: K. N. Browning, 6520 MSRB1, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0682 (E-mail: kirsteen{at}umich.edu).
10.1152/ajpgi.00322.2002
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Altschuler, SM,
Bao X,
Bieger D,
Hopkins DA,
and
Miselis RR.
Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts.
J Comp Neurol
283:
248-268,
1989[ISI][Medline].
2.
Andresen, MC,
and
Yang M.
Gadolinium and mechanotransduction of rat aortic baroreceptors.
Am J Physiol Heart Circ Physiol
262:
H1415-H1421,
1992
3.
Armour, JA,
Huang MH,
Pelleg A,
and
Sylven C.
Responsiveness of in situ canine nodose ganglion afferent neurones to epicardial mechanical or chemical stimuli.
Cardiovasc Res
28:
1218-1225,
1994[ISI][Medline].
4.
Aviado, DM,
and
Guevara AD.
The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes.
Ann NY Acad Sci
940:
48-58,
2001
5.
Benson, CJ,
Eckert SP,
and
McCleskey EW.
Acid-evoked currents in cardiac sensory neurons: a possible mediator of myocardial ischemic sensation.
Circ Res
84:
921-928,
1999
6.
Browning KN. Electrophysiological properties of identified
gastrointestinal sensory neurons of the rat nodose ganglion (Abstract).
Gastroenterology 122, Suppl 1: S1070.
2002.
7.
Canon, WB,
and
Leib CW.
The receptive relaxation of the stomach.
Am J Physiol
29:
267-273,
1911
8.
Carr, MJ,
Hunter DD,
Jacoby DB,
and
Undem BJ.
Expression of tachykinins in nonnociceptive vagal afferent neurons during respiratory viral infection in guinea pigs.
Am J Respir Crit Care Med
165:
1071-1075,
2002
9.
Chen, CY,
Ling Eh EH,
Horowitz JM,
and
Bonham AC.
Synaptic transmission in nucleus tractus solitarius is depressed by group II and III but not group I presynaptic metabotropic glutamate receptors in rats.
J Physiol
538:
773-786,
2002
10.
Cooper, E,
and
Shrier A.
Inactivation of A currents and A channels on rat nodose neurons in culture.
J Gen Physiol
94:
881-910,
1989[Abstract].
11.
Cunningham, JT,
Wachtel RE,
and
Abboud FM.
Mechanosensitive currents in putative aortic baroreceptor neurons in vitro.
J Neurophysiol
73:
2094-2098,
1995
12.
Cunningham, JT,
Wachtel RE,
and
Abboud FM.
Mechanical stimulation of neurites generates an inward current in putative aortic baroreceptor neurons in vitro.
Brain Res
757:
149-154,
1997[ISI][Medline].
13.
Drummond, HA,
Price MP,
Welsh MJ,
and
Abboud FM.
A molecular component of the arterial baroreceptor mechanotransducer.
Neuron
21:
1435-1441,
1998[ISI][Medline].
14.
Fox, EA,
and
Powley TL.
Longitudinal columnar organization within the dorsal motor nucleus represents separate branches of the abdominal vagus.
Brain Res
341:
269-282,
1985[ISI][Medline].
15.
Fueri, C,
Faudon M,
Hery M,
and
Hery F.
Release of serotonin from perikaya in cat nodose ganglia.
Brain Res
304:
173-177,
1984[ISI][Medline].
16.
Gebhart, GF,
Bielefeldt K,
and
Ozaki N.
Gastric hyperalgesia and changes in voltage gated sodium channel function in the rat.
Gut
51, Suppl1:
I15-I18,
2002[ISI][Medline].
17.
Glaum, SR,
and
Miller RJ.
Presynaptic metabotropic glutamate receptors modulate omega-conotoxin-GVIA-insensitive calcium channels in the rat medulla.
Neuropharmacology
34:
953-964,
1995[ISI][Medline].
18.
Grundy, D,
and
Scratcherd T.
Sensory afferents from the gastrointestinal tract.
In: The Gastrointestinal System: Motility and Circulation. Bethesda, MD: Am Physiol Soc, 1989, sect. 6, vol. I, pt. 1, chapt. 16, p. 593-620.
19.
Hajduczok, G,
Chapleau MW,
Ferlic RJ,
Mao HZ,
and
Abboud FM.
Gadolinium inhibits mechanoelectrical transduction in rabbit carotid baroreceptors. Implication of stretch-activated channels.
J Clin Invest
94:
2392-2396,
1994[ISI][Medline].
20.
Hamra, M,
McNeil RS,
Runciman M,
and
Kunze DL.
Opioid modulation of calcium current in cultured sensory neurons: µ- modulation of baroreceptor input.
Am J Physiol Heart Circ Physiol
277:
H705-H713,
1999
21.
Hay, M,
and
Kunze DL.
Glutamate metabotropic receptor inhibition of voltage-gated calcium currents in visceral sensory neurons.
J Neurophysiol
72:
421-430,
1994
22.
Hirning, LD,
Fox AP,
McCleskey EW,
Olivera BM,
Thayer SA,
Miller RJ,
and
Tsien RW.
Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons.
Science
239:
57-61,
1988[ISI][Medline].
23.
Holzer, HH,
and
Raybould HE.
Vagal and splanchnic sensory pathways mediate inhibition of gastric motility induced by duodenal distension.
Am J Physiol Gastrointest Liver Physiol
262:
G603-G608,
1992
24.
Irwin, RS,
and
Richter JE.
Gastroesophageal reflux and chronic cough.
Am J Gastroenterol
95:
S9-S14,
2000[ISI][Medline].
25.
Jafri, MS,
and
Weinreich D.
Substance P regulates Ih via a NK-1 receptor in vagal sensory neurons of the ferret.
J Neurophysiol
79:
769-777,
1998
26.
Jordan, D.
Central nervous pathways and control of the airways.
Respir Physiol
125:
67-81,
2001[ISI][Medline].
27.
Li, Y,
and
Owyang C.
Vagal afferent pathway mediates physiological action of cholecystokinin on pancreatic enzyme secretion.
J Clin Invest
92:
418-424,
1993[ISI][Medline].
28.
Lieberman, AR.
Sensory ganglia.
In: The Peripheral Nerve, edited by Landon DN.. London: Chapman & Hall, 1976, p. 188-278.
29.
Linz, P,
and
Veelken R.
Serotonin 5-HT(3) receptors on mechanosensitive neurons with cardiac afferents.
Am J Physiol Heart Circ Physiol
282:
H1828-H1835,
2002
30.
Lloyd, KCK,
Holzer HH,
Zittel TT,
and
Raybould HE.
Duodenal lipid inhibits gastric acid secretion by vagal, capsaicin-sensitive pathways in rats.
Am J Physiol Gastrointest Liver Physiol
264:
G659-G663,
1993
31.
McCann, MJ,
and
Rogers RC.
Oxytocin excites gastric-related neurons in rat dorsal vagal complex.
J Physiol
428:
95-108,
1990[Abstract].
32.
Mendelowitz, D,
Reynolds PJ,
and
Andresen MC.
Heterogeneous functional expression of calcium channels at sensory and synaptic regions in nodose neurons.
J Neurophysiol
73:
872-875,
1995
33.
Moore, KA,
Taylor GE,
and
Weinreich D.
Serotonin unmasks functional NK-2 receptors in vagal sensory neurons of the guinea-pig.
J Physiol
514:
111-124,
1999
34.
Moore, KA,
Undem BJ,
and
Weinreich D.
Antigen inhalation unmasks NK-2 tachykinin receptor-mediated responses in vagal afferents.
Am J Respir Crit Care Med
161:
232-236,
2000
35.
Myers, AC,
Kajekar R,
and
Undem BJ.
Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways.
Am J Physiol Lung Cell Mol Physiol
282:
L775-L781,
2002
36.
Oh, EJ,
and
Weinreich D.
Chemical communication between vagal afferent somata in nodose ganglia of the rat and the guinea pig in vitro.
J Neurophysiol
87:
2801-2807,
2002
37.
Pfrieger, FW,
Veselovsky NS,
Gottmann K,
and
Lux HD.
Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro.
J Neurosci
12:
4347-4357,
1992[Abstract].
37a.
Powley, TL,
and
Phillips RJ
Musings on the Wanderer: What's New in Our Understanding of Vago-Vagal Reflexes? I. Morphology and topography of vagal afferents innervating the GI tract.
Am J Physiol Gastrointest Liver Physiol
283:
G1217-G1225,
2002
38.
Rhim, H,
Glaum SR,
and
Miller RJ.
Selective opioid agonists modulate afferent transmission in the rat nucleus tractus solitarius.
J Pharmacol Exp Ther
264:
795-800,
1993[Abstract].
39.
Rogers, RC,
Hermann GE,
and
Travagli RA.
Brainstem pathways responsible for oesophageal control of gastric motility and tone in the rat.
J Physiol
514:
369-383,
1999
40.
Schwartz, GJ,
and
Moran TH.
Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal afferent signals in rat.
Am J Physiol Regul Integr Comp Physiol
274:
R1236-R1242,
1998
41.
Straub, RH,
Antoniou E,
Zeuner M,
Gross V,
Scholmerich J,
and
Andus T.
Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn's disease and ulcerative colitis.
J Neuroimmunol
80:
149-157,
1997[ISI][Medline].
42.
Thompson, GW,
Horackova M,
and
Armour JA.
Chemotransduction properties of nodose ganglion cardiac afferent neurons in guinea pigs.
Am J Physiol Regul Integr Comp Physiol
279:
R433-R439,
2000
43.
Travagli, RA,
and
Gillis RA.
Hyperpolarization-activated currents Ih and IKIR in rat dorsal motor nucleus of the vagus neurons, in vitro.
J Neurophysiol
71:
1308-1317,
1994
44.
Undem, BJ,
and
Weinreich D.
Electrophysiological properties and chemosensitivity of guinea pig nodose ganglion neurons in vitro.
J Auton Nerv Syst
44:
17-34,
1993[ISI][Medline].
45.
Yox, DP,
Stokesberry H,
and
Ritter RC.
Vagotomy attenuates suppression of sham feeding induced by intestinal nutrients.
Am J Physiol Regul Integr Comp Physiol
260:
R503-R508,
1991
46.
Zhuo, H,
Ichikawa H,
and
Helke CJ.
Neurochemistry of the nodose ganglion.
Prog Neurobiol
52:
79-107,
1997[ISI][Medline].