-Adrenergic receptor number in human lymphocytes is
inversely correlated with aerobic capacity
Nobuharu
Fujii1,
Sachiko
Homma2,
Fumio
Yamazaki3,
Ryoko
Sone4,
Takeshi
Shibata1,
Haruo
Ikegami5,
Kazuo
Murakami1, and
Hitoshi
Miyazaki1
1 Gene Experiment Center,
Institute of Applied Biochemistry, University of Tsukuba,
Tsukuba-City 305; 2 Research
Institute of Physical Fitness, Japan Women's College of Physical
Education, Tokyo 157; 3 School of
Health Science, University of Occupational and Environmental
Health, Kitakyushu 807;
4 Department of Exercise and
Health Science, Faculty of Education, University of Yamaguchi,
Yamaguchi 753; and
5 Department of Physical
Education, International Budo University, Katsuura 299-52, Japan
 |
ABSTRACT |
In the present
study, the relationships between
-adrenergic receptor (
-AR)
expression and aerobic capacity evaluated by maximal oxygen consumption
(
) and oxygen consumption level at ventilatory threshold
(
O2@VT) were investigated.
Seventeen physically untrained and 25 trained men participated in the
study. After supine resting, the peripheral blood was sampled for
preparation of lymphocytes, the model cell used to analyze the
-AR
state. The total number of
-AR in lymphocytes (
-ARtotal) was inversely
correlated with the
O2 max
(r =
0.368; P < 0.05) and the
O2@VT
(r =
0.359;
P < 0.05). Similar relationships were also observed between the number of
-AR in cell surface and
both
O2 max
(r =
0.491;
P < 0.05) and
O2@VT
(r =
0.498; P < 0.05). However, no correlation
was obtained between the number of
-AR in intracellular compartments
and either
O2 max or
O2@VT. The
2-AR mRNA level quantified by
the use of competitive reverse transcription-polymerase chain reaction
was inversely correlated with
O2@VT
(r =
0.567;
P < 0.05) and positively correlated with
-ARtotal
(r = 0.521;
P < 0.05). These findings
suggest that the
-AR number in lymphocytes is inversely correlated
with aerobic capacity. This relationship may be explained by
downregulation of
-AR, including internalization with subsequent
degradation of the receptors and inhibition of the
-AR biosynthesis.
catecholamine; downregulation; competitive reverse
transcription-polymerase chain reaction
 |
INTRODUCTION |
PHYSICAL TRAINING is associated with cardiovascular
adaptations such as bradycardia at rest (33) and lower heart rate and blood pressure responses during submaximal exercise (7). These phenomena may be explained at least in part by a decrease in the number
of myocardial
-adrenergic receptors (
-AR) causing reduced sympathomimetic effects (30). In in vitro experiments, prolonged agonist exposure induced the loss of
-AR at the cell surface (35).
In addition, 24-h integrated plasma catecholamine concentrations are
greater in physically trained men than in untrained men (9). Therefore,
physical training seems to induce the loss of
-AR and the
attenuation of cellular responsiveness to sympathoadrenomedullary activity.
The number of
-AR, the responsiveness of
-AR to its agonist, and
the content of stimulatory guanine nucleotide-binding protein in human
lymphocytes are correlated with those in the myocardium (4, 16).
Consequently, in humans, the effects of physical training on
-AR
have been studied using lymphocytes derived from peripheral blood as a
model cell (22). However, so far, conflicting results have been
obtained. Butler et al. (5) and Ohman et al. (29) found a significant
reduction in the
-AR number induced by training, but, conversely,
several other investigators observed increased
-AR number in trained
subjects (20, 23). Moreover, Frey et al. (10) failed to demonstrate any
relation between
-AR number and physical fitness. In this regard,
Jost et al. (17) reported that long-distance runners and swimmers had
fewer
-AR during the endurance training period (i.e., relatively
aerobic exercise training) compared with sedentary individuals, but
slightly more
-AR were seen during the high-intensity training
period (i.e., relatively anaerobic exercise training). Their report
indicates a possibility that the controversial results acquired in
previous studies may have arisen due to the difference in the exercise training conditions or the change in physiological functions such as
the aerobic energy system after training variation. Thus different conclusions would be obtained by various research groups, depending on
the variation of physical training such as endurance training and
high-intensity training, even though the same types of athletes might
have constituted the subjects of the studies. If so, group comparison
would not be a suitable design for this kind of study. Therefore, it is
possible that some relations between the physical training and the
-AR number would be detected by characterizing the aerobic capacity
in individual subjects.
The present study was thus conducted to clarify the effect of physical
training on the
-AR number in human lymphocytes by examining this
effect as a function of aerobic capacity evaluated by maximal oxygen
consumption (
O2 max)
and oxygen consumption level at ventilatory threshold
(
O2@VT). To obtain more
detailed information on the underlying mechanism of the change in the
-AR number with aerobic capacity, we examined the number of
-AR
in both the cell surface
(
-ARsurface) and
intracellular compartment (
-ARintra) in intact
lymphocytes by measuring the binding of the lipophilic radioligand
[125I]iodocyanopindolol
([125I]ICYP) in the presence and
absence of the hydrophilic or lipophilic nonradioactive antagonist.
Moreover, we used the competitive reverse transcription (RT)-polymerase
chain reaction (PCR) method, which is effective in quantifying the mRNA
level in small samples such as the lymphocytes in blood derived from
human subjects, to elucidate the effects of physical training on the
-AR mRNA level.
 |
METHODS |
Subjects. Seventeen physically
untrained men with age range of 20-27 yr and 25 physically trained
men with age range of 18-22 yr participated in this study after
having given written informed consent. The trained subjects were
collegiate long-distance runners (n = 13), short-distance runners (n = 6),
and baseball players (n = 6). The
untrained men were sedentary or participated only in leisure sports.
None of them was receiving any medication, and a thorough clinical
examination failed to demonstrate any abnormalities in their health.
Experimental protocol. An indwelling
catheter with a three-way stopcock was inserted into a forearm vein.
After the subject lay supine for 20 min in a quiet room, a 40-ml blood
sample was withdrawn for preparation of lymphocytes and determination
of plasma catecholamine concentrations. The total number of
-AR in
lymphocytes (
-ARtotal) and
plasma catecholamine concentrations were quantified in all subjects,
except that in one subject the plasma catecholamine concentrations
could not be measured because of insufficient blood sampling. The
-ARsurface and
-ARintra were analyzed in 24 subjects (9 untrained men, 7 long-distance runners, 4 short-distance
runners, and 4 baseball players), and the
2-AR mRNA level was assayed in
18 subjects (8 untrained men, 6 long-distance runners, 2 short-distance
runners, and 2 baseball players) because of limitation on the amount of
blood that could be obtained from a subject. For measurement of
-ARtotal,
-ARsurface and
-ARintra,
2-AR mRNA level, and plasma
catecholamine concentrations, 24, 12, 12, and 4 ml of blood were used,
respectively. After blood was sampled, the subject performed bicycle
ergometry in a sitting position until exhaustion. Every 2 min, the
workload was increased by 20 watts in untrained and 25 watts in trained
subjects. Respiratory gas analysis was performed with an Oxycon-4
(Mijnhard) and was used to determine minute ventilation (VE), minute
oxygen consumption (
O2),
and minute carbon dioxide production
(
CO2). These parameters were averaged over the last 30 s in each stage and supplied for the
determination of
O2 max and
O2@VT.
Determination of
O2 max and
O2@VT.
O2 max was determined
as the
O2 averaged over the
last 30 s in the final stage. Ventilatory threshold was determined by
visual inspection after consideration of events during incremental
exercise, as a deviation of the incremental rate of VE plotted against
O2 from the linear
increase, and an increase of
VE/
O2 plotted against
O2 without an increase of
VE/
CO2 (8).
Measurement of the lymphocyte
-AR
number. Lymphocytes were prepared by the method of
Bøyum (2). Whole blood was diluted with an equal volume of
phosphate-buffered saline (PBS), and an aliquot (17 ml) was then
carefully layered on 12 ml of Ficoll-Paque (Pharmacia). The tubes were
centrifuged at 400 g for 40 min. After removal of the plasma, the lymphocytes were harvested carefully, washed
three times with 10 vol of PBS, and then resuspended in 10 mM Tris, 154 mM NaCl, and 0.55 mM ascorbic acid, pH 7.4 (buffer A). For binding assay, intact lymphocytes (1 × 106 cells) were incubated with
various concentrations (1-180 pM) of
[125I]ICYP in 0.5 ml of
buffer A containing 0.05% bovine
serum albumin (BSA). Propranolol (2 µM) and CGP-12177A (2 µM) were
used to detect nonspecific binding (26). The difference in
[125I]ICYP binding with and
without the hydrophobic ligand propranolol represents the total
specific binding to
-ARtotal.
The difference in binding with and without the hydrophilic ligand
CGP-12177A (Ciba-Geigy) indicates the specific binding to
-ARsurface. The specific
binding to
-ARintra was
obtained from the difference between the binding to
-ARtotal and to
-ARsurface. The incubation was
carried out at 37°C for 40 min and stopped by placing the tubes on
ice and adding 2 ml of ice-cold PBS containing 0.1% BSA to each tube.
The samples were filtered through Whatman GF/D filters, and each filter
was washed two times with an additional 3 ml of PBS. The radioactivity
of the filters was determined in a gamma counter (ARC1000M; Aloka). The
binding data were analyzed according to the method of Scatchard (32).
Isolation of total RNA. Total cellular
RNA was isolated by Isogen (Nippon Gene) containing guanidinium
isothiocyanate and phenol (6). Briefly, aliquots of the cells were
lysed by pipetting in a mixture containing Isogen and chloroform. After
centrifugation at 4°C, the aqueous phase was precipitated in
isopropanol. The RNA pellet was washed one time in 70% ethanol, dried,
and dissolved in diethylpyrocarbonate-treated water. Genomic DNA was
removed by digestion with RNase-free DNase I (Nippon Gene) for 1 h at 37°C. RNA was checked by 1% agarose gel
electrophoresis in the presence of 0.66 M formaldehyde. The purity of
RNA was checked spectrophotometrically by the ratio of 260 nm to 280 nm
and electrophoretically by the presence of intense bands of 18S and 28S
RNA. The yield was determined spectrophotometrically at 260 nm.
Preparation of a deletion-mutated
-AR
cDNA fragment for competitive RT-PCR analysis. A 401-bp
fragment containing part of the coding region of the human
2-adrenergic receptor
(
2-AR) gene (73-473;
nucleotides numbered sequentially from the translation initiation site)
was amplified with the following primers:
5'-ACGCAGCAAAGGGACGAG-3' (5'-sense primer) and
5'-CACACCATCAGAATGATCAC-3' (3'-antisense primer; see
Ref. 11). These fragments were phosphorylated at their 5'-ends
and inserted into the EcoR V site of
pBluescript KS(+) (Stratagene). The resultant plasmid was digested with
Msc I and
BstE II, blunt-ended with T4 DNA
polymerase, and self-ligated to generate a plasmid containing the
insert lacking the Msc
I-BstE II fragment (62 bp). This
plasmid was amplified by PCR using the primers described above, and the
resultant deletion-mutated
2-AR cDNA (339 bp) was resolved by polyacrylamide gel electrophoresis. After
recovery, the cDNA fragment was quantified and used as a competitor for
competitive RT-PCR.
Competitive RT-PCR. Total RNA (1.8 µg) was reverse transcribed to cDNA in the presence of 10 U/µl
cloned Moloney murine leukemia virus reverse transcriptase (GIBCO-BRL),
125 µM each of dNTPs, 10 mM dithiothreitol, 2 U/µl ribonuclease
inhibitor (Takara), 5 ng/µl pd(N)6 random primers, and RT buffer (50 mM Tris · HCl, pH 8.3, 75 mM KCl, and 3 mM
MgCl2) to a total volume of 20 µl. A corresponding aliquot of cDNA mixture synthesized from 100 ng of total RNA was subjected to competitive PCR analysis using the same
primers (1 µM each) described above in the presence of various amounts of the competitors to quantify the PCR products. Reaction solution for PCR consisted of 10 mM Tris · HCl, pH
8.3, 50 mM KCl, 1.5 mM MgCl2,
0.01% (wt/vol) gelatin, 125 µM each of dNTPs, 0.01 µCi/µl
[
-32P]dCTP, and
0.02 U/µl Amplitaq polymerase (Perkin-Elmer). PCR was performed by 28 cycles of denaturation at 94°C for 1 min, annealing at 56°C for
1 min, and extension at 72°C for 1.5 min. Thereafter, the
incubation was continued at 72°C for 8.5 min to complete the
polymerization. The PCR products were size-fractionated on 5%
acrylamide gels. The gels were dried and analyzed using a
computer-based imaging system (BAS 2000; Fuji). The amount of
2-AR mRNA was then calculated
by extrapolating from the intersection of the curves, where the amounts
of target and competitor were equivalent [log(target/competitor) = 0] to the x-axis (12). Resultant values of
2-AR mRNA
were normalized with the RT-PCR products of glyceraldehyde-6-phosphate
dehydrogenase mRNA quantified in an independent experiment series (12).
Determination of
-AR subtypes
expressed in human lymphocytes by RT-PCR. To determine
the
-AR subtypes expressed in lymphocytes, RT-PCR was carried out
under the same conditions as described above except that the competitor
was not added, and denaturing, annealing, and extension reactions
proceeded 30 times at 94°C for 1 min, 50°C for 1 min, and
72°C for 1.5 min, respectively. The following PCR oligonucleotide
primers that hybridize to the conserved sequence among the human
1-adrenergic receptor
(
1-AR),
2-AR, and
3-adrenergic receptor
(
3-AR) cDNAs were used: sense 5'-GTCTCCTTCTACGTTCC-3' and antisense
5'-AAGAAGGGCATCCAGCAGAG-3' (Fig.
1A).
Amplified cDNAs of
1-,
2-, and
3-ARs should give 337-, 254-, and 296-bp fragments, respectively. These products were
electrophoretically separated on 4% acrylamide gels. The gels were
dried and analyzed using a computer-based imaging system (BAS 2000;
Fuji).

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Fig. 1.
Subtype distribution of -adrenergic receptors ( -AR) in human
lymphocytes. RT-PCR was performed by using the oligonucleotide primers
that hybridize the conserved sequence among the human
1-,
2-, and
3-AR cDNA.
A: nucleotide sequences of the human
1-,
2-, and
3-AR cDNA that are hybridized
by PCR primers. Incomplementary sequences to PCR primers are boxed.
Nucleotides are numbered sequentially from the translation initiation
site. B: size fraction of -AR
subtype cDNAs amplified from human lymphocyte RNA by RT-PCR.
C: quantitative comparison of the mRNA
expression level of -AR subtypes in lymphocytes.
|
|
Determination of plasma
catecholamines. Plasma norepinephrine and epinephrine
concentrations were quantified using high-performance liquid
chromatography with electrochemical detection (13).
Statistics. Pearson's formula was
used to calculate the correlation coefficients. Comparisons among
groups were made by one-way ANOVA. Probability value of <0.05 was
considered significant.
 |
RESULTS |
We first examined the subtype proportion of
-AR in human lymphocytes
by RT-PCR using oligonucleotide primers that hybridize to the conserved
sequence among the human
1-,
2-, and
3-AR cDNAs (Fig.
1A). Because the melting
temperature of these primers to the cDNA of each subtype is identical,
radioactivity of resultant PCR products that are size-fractionated by
electrophoresis indicates the mRNA level of each
-AR subtype. As
shown in Fig. 1, B and C,
2-AR mRNA level was
predominant. In contrast, little amount of
1-AR mRNA (~1.5% of the
total specific radioactivity) and no
3-AR mRNA were detected.
Similar results were also obtained from separate PCR amplification of
each
-AR subtype using specific primers for them in different
reaction tubes (data not shown). Therefore, predominant amplification
of
2-AR mRNA was not
artificially caused by the coamplification of all three subtype
fragments in a single reaction tube. These results strongly demonstrate
that almost every
-AR is the
2-AR subtype in human
lymphocytes.
As presented in Fig. 2, the
-ARtotal was inversely
correlated with
O2 max
and
O2@VT. Similar
relationships between the
-ARsurface and both
O2 max and
O2@VT were also
observed (Fig. 3). In contrast, no
correlation was obtained between
-ARintra and either
O2 max or
O2@VT (Fig.
4). The
2-AR mRNA level was inversely
correlated with
O2@VT (Fig.
5) and tended to be correlated with
O2 max
(P = 0.07). As indicated in Fig.
6, the
-ARtotal was positively
correlated with the
2-AR mRNA
level.

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Fig. 2.
Scatterplots of the relation of the total number of -AR in
lymphocytes ( -ARtotal) in
blood samples obtained at rest with maximal oxygen consumption
( O2 max;
A) and oxygen consumption level at
ventilatory threshold
( O2@VT;
B). Lymphocytes were prepared from
blood samples obtained at rest just before bicycle ergometry. ,
Untrained men; x, baseball player; , short-distance runner; ,
long-distance runner.
|
|

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Fig. 3.
Scatterplots of the relation of the number of lymphocyte -AR in cell
surfaces ( -ARsurface) with
O2 max
(A) and
O2@VT
(B). Lymphocytes were prepared from
blood samples obtained at rest just before bicycle ergometry. ,
Untrained men; x, baseball player; , short-distance runner; ,
long-distance runner.
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Fig. 4.
Scatterplots of the relation of the number of lymphocyte -AR in
intracellular compartments
( -ARintra) with
O2 max
(A) and
O2@VT
(B). Lymphocytes were prepared from
blood samples obtained at rest just before bicycle ergometry. ,
Untrained men; x, baseball player; , short-distance runner; ,
long-distance runner.
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Fig. 5.
Scatterplots of the relation of the lymphocyte
2-AR mRNA level with
O2 max
(A) and
O2@VT
(B). Lymphocytes were prepared from
blood samples obtained at rest just before bicycle ergometry. ,
Untrained men; x, baseball player; , short-distance runner; ,
long-distance runner.
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Fig. 6.
Relationship between -ARtotal
and 2-AR mRNA level. ,
Untrained men; x, baseball player; , short-distance runner; ,
long-distance runner.
|
|
Table 1 shows the group comparison of the
aerobic capacity and the number of
-AR in lymphocytes. Significant
differences were observed for
O2 max and
O2@VT among the
groups by ANOVA. However, in contrast to the results of cross-sectional
analysis (Figs. 2-5), no statistically significant differences for
the measurements on the
-AR number and on the
-AR mRNA level were
seen among the groups, except that
-ARtotal tended to be different
(P < 0.15).
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Table 1.
Comparisons of the aerobic capacity and the -adrenergic
receptor expression level in lymphocytes among the groups
|
|
The results of correlation analysis of the relationship of each plasma
catecholamine concentration with
-ARtotal,
-ARsurface,
-ARintra, and
2-AR mRNA level are summarized
in Table 2. A significant inverse
correlation between the plasma epinephrine concentration and the
-ARsurface was found. Plasma
epinephrine concentration tended to be correlated with
-ARtotal
(P = 0.07). A significant
relationship between the plasma epinephrine concentration and the
2-AR mRNA level could not be
demonstrated. The plasma norepinephrine concentration showed no
correlation with any of the
-ARtotal,
-ARsurface,
-ARintra, and
2-AR mRNA levels.
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Table 2.
Correlation coefficients for plasma catecholamine concentrations with
-adrenergic receptor number and mRNA level
|
|
No significant correlations were seen between
O2 max and both plasma
epinephrine (r = 0.174) and plasma
norepinephrine (r = 0.226)
concentrations and between
O2@VT and both plasma
epinephrine (r = 0.222) and plasma
norepinephrine (r = 0.146)
concentrations.
 |
DISCUSSION |
In the present study, lymphocyte
-ARtotal was
inversely correlated with
O2 max and
O2@VT. These results support
the assertion by Butler et al. (5) and by Ohman et al. (29) that the
-AR number in human lymphocytes is reduced by physical training. We also found that the inverse relationships were dependent on the change
in the
-ARsurface but not on
that in the
-ARintra.
Furthermore, this is the first report indicating a significant inverse
correlation between the
2-AR
mRNA level and
O2@VT and a
positive association between the
2-AR mRNA level and
-ARtotal. These results suggest that the reduction of
-AR number is involved with the clonic adaptation to aerobic exercise.
Continued exposure of cells to
-adrenergic agonists in vitro leads
to a decrease in the number of functional
-AR in the plasma membrane
in a manner indicating the loss of receptors from the cell surface
(15). Downregulation and sequestration have been identified as two
phenomena that contribute to the agonist-mediated decrease in receptor
number from the cell surface (35). Downregulation has been hypothesized
to involve accelerated receptor degradation, presumably in lysosomes,
as well as decreased receptor biosynthesis. Sequestration has been
proposed to result from internalization of receptors for reactivation
and recycling of desensitized receptors from the cell surface to the
intracellular compartment depot in which receptors are not degraded.
Because there was a significant inverse relationship between the plasma
epinephrine concentration and
-ARsurface in this study, it is
possible that plasma epinephrine promotes the internalization of
-AR
from the cell surface to the intracellular space. If this
internalization occurred as an event of sequestration,
-ARintra would increase and be
positively correlated with plasma epinephrine. In this study, however,
no significant correlation was found between the two, suggesting that
plasma epinephrine may be associated with the degradation of
-AR.
Dela et al. (9) reported that the 24-h integrated plasma catecholamine
concentrations were two times as high in physically trained as in
untrained subjects. Therefore, our findings suggest that the increased
epinephrine secretion induced by daily training is associated with the
decrease in
-ARsurface due
to the internalization with subsequent degradation of
-AR.
Furthermore, the increase in the plasma epinephrine concentration,
rather than plasma norepinephrine concentration, appears to be
associated with this phenomenon.
The significant relationship between
-ARtotal and
2-AR mRNA level observed in
this study suggests that the suppression of biosynthesis of
-AR
associated with the reduction in mRNA level also contributes to the
decrease in
-ARtotal after
physical training. It is known that chronic stimulation of cells with
-adrenergic agonist reduces the steady-state level of
2-AR mRNA in vitro (14).
However, in our in vivo study, the plasma catecholamine concentrations
were not correlated with
2-AR
mRNA level. Therefore, other factors may contribute to the reduction of
the
2-AR mRNA level. It should
be noted that the regulation of
2-AR mRNA level might be
expected to be a reflection of the chronic effect of training and thus
of the chronic change in the concentrations of catecholamines. The
measurement of 24-h integrated plasma catecholamine concentrations as
reported by Dela et al. (9), therefore, may be necessary for examining
the effect of catecholamines on the
2-AR mRNA in vivo.
Jost et al. (17) reported that long-distance runners and swimmers had
fewer
-AR during the endurance training period compared with
sedentary individuals, but slightly more
-AR were seen during the
high-intensity training period. Their finding indicates that the
difference in the energy supply system recruited during exercise training may affect the expression of
-AR. Thus we hypothesized that
the different conclusions obtained by various research groups (5, 10,
20, 23, 29) may depend on the variation of physical training such as
endurance training and high-intensity training, even though the same
types of athletes might have constituted the subjects of the studies.
In this study, no significant difference of the
-AR number among the
groups was obtained by group comparison analysis using ANOVA. In
contrast, inverse relationships between the
-AR number and the
aerobic capacity were detected by examining the change in
-AR number
and mRNA level as a function of aerobic capacity in a heterogeneous
group of subjects who had wide distribution of
O2 max and
O2@VT. These results may
support our hypothesis.
Because there is a report (21) indicating that
2-AR couples to adenylyl
cyclase with a greater efficacy than
1-AR,
2-AR may have an important role
in regulating the cardiac function despite the lower expression level
compared with
1-AR in human heart (3). Actually, overexpression of human
2-AR in heart of transgenic
mice (25) exhibits functional changes more drastically than
overexpression of human
1-AR
(1). Therefore, if the regulation of the
2-AR content in lymphocytes
reflects that in the heart, lymphocyte
2-AR analysis may provide
significant information about the role of the
-adrenergic system in
the cardiac functions. Although we have no direct evidence on whether
the change in the content of myocardial
2-AR as a result of exercise
training parallels that in lymphocytes in this study, Michel et al.
(24) reported that lymphocyte
2-AR number significantly
correlates with the number of myocardial
2-AR under basal conditions.
Lymphocytes comprise distinct subsets that differ in the number of
-AR (19). This feature raises the possibility that the change in
composition of these subsets may be induced by physical training. Some
reports suggest that chronic physical training induces no change of the
lymphocyte subset distribution in human subjects (18, 27, 28). However,
a few investigators have found changes in the percentages of the
subsets associated with physical training, i.e., increased natural
killer cell population in endurance-trained men (31) and increased
T-suppressor/cytotoxic cell population and decreased T-helper cell
population in distance runners (34). Our results might underestimate
the effects of physical training on downregulation of
-AR, since
among lymphocytes the natural killer cell population has the most and
the T-helper cell population the least
-AR.
In conclusion, we found an inverse relationship between the
-AR number in human lymphocytes and the aerobic capacity evaluated by
O2 max and
O2@VT. We consider that this
inverse relationship may result from downregulation of the
-AR,
including internalization with subsequent degradation of the receptors
and inhibition of the
-AR biosynthesis after aerobic physical
training.
 |
ACKNOWLEDGEMENTS |
We are grateful to Dr. Yoshiharu Nabekura at the University of
Tsukuba for managing the subjects. We thank Dr. Tetsuya Izawa at the
Tokyo Metropolitan University for critical discussion. We appreciate
the donation of CGP-12177A by K. G. Hofbauer and Dr. H. Kaufmann
(Ciba-Geigy, Basel).
 |
FOOTNOTES |
This study was supported in part by grants from the Meiji Life
Foundation of Health and Welfare, Japan.
Address for reprint requests: H. Miyazaki, Gene Experiment Center,
Univ. of Tsukuba, Tsukuba-City, Ibaraki 305, Japan.
Received 11 August 1997; accepted in final form 19 February 1998.
 |
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