Postglomerular vasoconstriction induced by dopamine D3 receptor activation in anesthetized rats

Gerd Luippold, Swetlana Schneider, Volker Vallon, Hartmut Osswald, and Bernd Mühlbauer

Department of Pharmacology, University of Tübingen, D-72074 Tübingen, Germany


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

In the present study we investigated the renal hemodynamic effects of dopamine D3 receptor activation by R(+)-7-hydroxy-dipropylaminotetraline (7-OH-DPAT) in thiopental-anesthetized Sprague-Dawley rats. In clearance experiments infusion of 7-OH-DPAT (0.01-1.0 µg · kg-1 · min-1) dose-dependently elevated glomerular filtration rate (GFR) without affecting mean arterial blood pressure (MAP). In renal blood flow experiments 7-OH-DPAT infusion (1.0 µg · kg-1 · min-1) increased GFR by 16 ± 2%, associated with an unexpected fall in renal blood flow by 20 ± 3% and a significant elevation of renal vascular resistance by 18 ± 3%. The renal hemodynamic changes were not influenced by pretreatment with the D2-receptor antagonist S(-)-sulpiride but were completely abolished during D3 receptor inhibition by 5,6-dimethoxy-2-(di-n-propylamino)indane (U-99194A). In micropuncture experiments 7-OH-DPAT (1.0 µg · kg-1 · min-1) significantly elevated stop-flow pressure measured in the early proximal tubules and reduced hydrostatic pressure at the first branching point of the efferent arteriole without altering MAP. We conclude from these data that pharmacological activation of dopamine D3 receptors affects renal hemodynamics in anesthetized rats by preferential postglomerular vasoconstriction.

R(+)-7-hydroxy-dipropylaminotetraline; 5,6-dimethoxy-2-(di-n-propylamino)indane; S(-)-sulpiride; micropuncture experiments; renal hemodynamics


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

DOPAMINE RECEPTORS ARE INVOLVED in the regulation of cardiovascular and renal function. The five dopamine receptor subtypes identified so far are divided into two subfamilies: the D1-like receptor, including the D1 and the D5 receptor, and the D2-like receptor, among which D2, D3, and D4 receptors are counted (16). In the rat kidney D1-like receptors were described, by using polyclonal antisera, in the renal vasculature, the juxtaglomerular apparatus, the proximal and distal tubule as well as the cortical collecting duct (3). D2-like receptors have been suggested, by means of radioligand binding and pharmacological studies presynaptically on sympathetic nerve terminals in the adventitia of the renal vasculature and in the glomerulus (5). Very recently, immunohistochemical studies on the D3 receptor protein identified this receptor in the proximal and distal tubules, cortical collecting ducts, glomeruli, and renal arteries (4). Previous studies on the influence of the dopaminergic system on renal function, mainly focused on the D1 and D2 receptor subtypes, revealed conflicting results. Reasons for the discrepant observations might be differences in species and in type of experiments in conscious or anesthetized animals. The level of extracellular volume expansion appears, in addition, to modulate the renal actions of dopamine (8). Another reason for divergent results may be the involvement of the other dopamine receptors, i.e., D3, D4, or D5, the mRNA of which has been demonstrated in the mammalian kidney (6, 11, 12). Recently, we reported that pharmacological D3 receptor activation with the selective R(+) enantiomer of 7-hydroxy-dipropylaminotetraline (7-OH-DPAT) induced a significant diuresis, natriuresis, and an increase in glomerular filtration rate (GFR) (9). These data prompted us to elucidate the mechanisms by which D3 receptors might influence renal hemodynamics. In anesthetized rats, the effects of 7-OH-DPAT on renal hemodynamics were investigated in clearance as well as renal blood flow (RBF) experiments and micropuncture studies.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Experiments were performed in male Sprague-Dawley rats (Charles River, Sulzfeld, Germany) weighing 240-280 g. Rats had free access to standard rat chow (Altromin 1320, Altromin, Lage, Germany) and tap water.

Clearance experiments. Rats were anesthetized with an intraperitoneal injection of 80 mg/kg thiopental sodium (Byk Gulden, Konstanz, Germany) and placed on a temperature-controlled heated table (RT, Effenberger, Munich, Germany) to maintain the body temperature at 37.2°C. After tracheostomy, two polyethylene (PE) catheters were inserted into the right jugular vein for intravenous (iv) infusion. The left carotid artery was catheterized for withdrawal of blood samples and continuous monitoring of blood pressure (WK 280, WKK, Kaltbrunn, Switzerland). After suprapubic incision, a PE catheter was placed into the bladder and served for collection of urine. After the end of preparation the animals were allowed to reach steady-state conditions, defined by stable systemic hemodynamics and constant urinary flow rate, which was achieved within 60-90 min. Via the first iv catheter isotonic (0.85%) saline (NaCl) containing [3H]inulin (1 µCi/ml) was infused at a rate of 0.6 ml/h throughout the entire experiment for assessment of GFR. Via the second iv catheter NaCl was infused at a rate of 2.4 ml/h for completion of two baseline clearance periods. Thereafter, the D3 receptor agonist 7-OH-DPAT (0.01, 0.03, 0.1, 0.3, 1.0, or 3.0 µg · kg-1 · min-1; Biotrend, Cologne, Germany) dissolved in NaCl was infused via the second catheter at the same infusion rate (n = 3-6/dose). Ten minutes after initiation of the 7-OH-DPAT infusion, two experimental clearance periods were performed. Urine was collected in 20-min periods, and blood samples (180 µl each) were drawn at the midpoint of each clearance period.

RBF experiments. Anesthetic procedures and surgery were the same as described in clearance experiments. The arterial PE catheter was inserted into the left femoral artery. In addition, after flank incision the hilus of the left kidney was exposed, and an electromagnetic blood flow transducer connected to a flowmeter (Carolina Medical Electronics, King) was fitted around the left renal artery. During careful preparation of the kidney hilus all visible nerves were left intact. Both the urinary bladder and the left ureter were cannulated to maintain free urine flow. After completion of the surgical procedures, the animals were allowed to stabilize for 90 min before the measurements were started. [3H]inulin (1 µCi/ml) dissolved in isotonic NaCl was infused as described above. With the exception of the vehicle group, this infusion contained either the specific D3-receptor antagonist 5,6-dimethoxy-2-(di-n-propylamino)indane (U-99194A; 10 µg · kg-1 · min-1; Research Biochemicals International) or the D2 antagonist S(-)-sulpiride (SUL; 150 µg · kg-1 · min-1; Sigma Chemical, Deisenhofen, Germany). Isotonic NaCl was infused via the second iv catheter at a rate of 2.4 ml/h, and two baseline collection periods were carried out. Thereafter, all groups (n = 8 each) received 7-OH-DPAT (1 µg · kg-1 · min-1) dissolved in isotonic NaCl at the same infusion rate. Ten minutes after onset of the 7-OH-DPAT infusion, two 20-min clearance periods were performed. Blood samples were drawn at the midpoint of each collection period, and RBF was determined at the same time.

Micropuncture experiments. Rats were anesthetized with thiobutabarbital (100 mg/kg ip; Research Biochemicals International). Surgical preparation was similar to that described for RBF experiments. Additionally, the left kidney was exposed, freed of connective tissue, and immobilized in a lucite cup. The kidney was covered with prewarmed paraffin oil. Both the urinary bladder and the left ureter were cannulated to maintain free urine flow. On completion of the surgical preparation, the animals were allowed to stabilize for 90 min before micropuncture experiments were started. An estimation of glomerular capillary pressure was assessed by measuring stop-flow pressure (SFP) in the early proximal tubules. After identification of nephron configuration, an immobile wax block was injected into the early proximale tubule. A micropipette (2-3 µm outer diameter) filled with NaCl (1.5 mol/l) and connected to a servo-nulling device (World Precision Instruments, New Haven, CT) was inserted upstream of the wax block to monitor early proximal SFP. Hydrostatic pressure in the efferent arterioles was assessed by puncturing the superficial peritubular capillaries at the first branching point (star vessels). These micropuncture experiments were carried out in a paired way; i.e., the situation of the tubules and star vessels was depicted by a drawing, and the same sites were repunctured during 7-OH-DPAT infusion. In four animals SFP or hydrostatic pressure in the peritubular capillaries was monitored continuously before and during 7-OH-DPAT infusion. At baseline, animals were infused with isotonic (0.85%) NaCl (3.0 ml/h), whereas in the following experimental period neither NaCl (time controls) nor 7-OH-DPAT (1 µg · kg-1 · min-1) was infused at the same infusion rate.

Analyses and calculations. Arterial blood samples were analyzed for hematocrit. [3H]inulin radioactivity in plasma and urine was measured by a liquid scintillation counter (2550 TR, Canberra Packard, Frankfurt, Germany). GFR was determined by the renal clearance of inulin. Renal vascular resistance (RVR) and filtration fraction (FF) were calculated according to the standard formula.

Statistical methods. To evaluate the effects of 7-OH-DPAT on systemic and renal hemodynamics, the statistical significance of the differences between baseline (NaCl infusion) and experimental periods (7-OH-DPAT infusion) within groups was assessed by the paired two-sided t-test. All values are presented as means ± SE. P values <0.05 were considered to be statistically significant.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Clearance experiments. As shown in Fig. 1 and Table 1, 7-OH-DPAT infusion increased GFR dose dependently up to a maximum response of 20 ± 2% (ED50 = 0.09 µg · kg-1 · min-1) whereas mean arterial blood pressure (MAP) was not altered. Heart rate (HR) remained unchanged by 7-OH-DPAT up to 0.3 µg · kg-1 · min-1 and was slightly but significantly decreased during infusion of 1.0 µg · kg-1 · min-1 (Table 1). Because 3 µg · kg-1 · min-1 of 7-OH-DPAT markedly influenced systemic hemodynamics (Table 1), all further experiments were performed at 1.0 µg · kg-1 · min-1.


View larger version (18K):
[in this window]
[in a new window]
 
Fig. 1.   Dose-response curve describing effect of R(+)-7-hydroxy-dipro-pylaminotetraline (7-OH-DPAT) on glomerular filtration rate (GFR) in anesthetized rats as percent change from baseline values (means ± SE; n = 3-6/dose). Curve was heuristically fitted to a logistic sigmoid equation. ED50, dose at half-maximal response.


                              
View this table:
[in this window]
[in a new window]
 
Table 1.   Characteristics of clearance experiments

RBF experiments. In rats of the vehicle group (VHC), 7-OH-DPAT infusion (1.0 µg · kg-1 · min-1) significantly increased GFR by 16 ± 2% compared with baseline. RBF, in contrast, was reduced by 20 ± 3% (Fig. 2). These effects were paralleled by a significant increase in RVR and FF by 18 ± 3 and 36 ± 5%, respectively (Fig. 3). These changes in renal hemodynamics were not associated with an alteration in HR or MAP (Table 2). Pretreatment with SUL did not affect the renal response to 7-OH-DPAT: GFR was significantly elevated by 18 ± 5%, and RBF was reduced by 22 ± 3%. Thus 7-OH-DPAT infusion induced an increase in RVR and FF by 19 ± 3 and 40 ± 6%, respectively (Fig. 3), whereas MAP and HR were not affected during the entire experiments (Table 2). In contrast to these results, pretreatment with U-99194A competely abolished the 7-OH-DPAT-induced renal hemodynamic effects (Figs. 2 and 3). In these experiments, 7-OH-DPAT slightly lowered MAP and HR compared with baseline (Table 2).


View larger version (12K):
[in this window]
[in a new window]
 
Fig. 2.   Effect of 7-OH-DPAT on GFR (A) and renal blood flow (RBF; B) dependent on pretreatment with vehicle (VHC), S(-)-sulpiride (SUL) or U-99194A (UAM). Depicted are absolute values of 7-OH-DPAT infusion (filled bars) compared with baseline measurement (isotonic saline; open bars). Data are means ± SE and expressed per 1 kidney; n = 8/group. * P < 0.05 vs. baseline period.



View larger version (12K):
[in this window]
[in a new window]
 
Fig. 3.   Effect of 7-OH-DPAT on filtration fraction (FF; A) and renal vascular resistance (RVR; B) dependent on pretreatment with VHC, SUL, or UAM. Depicted are absolute values of 7-OH-DPAT infusion (filled bars) compared with baseline measurement (isotonic saline; open bars). Data are means ± SE and expressed per 1 kidney; n = 8/group. * P < 0.05 vs. baseline period.


                              
View this table:
[in this window]
[in a new window]
 
Table 2.   Characteristics of renal blood flow experiments

Micropuncture experiments. During baseline, SFP measured in the early proximal tubules (n = 5 rats/8 tubules) as an indicator of glomerular capillary pressure was 34.8 ± 0.9 mmHg, and hydrostatic pressure in the efferent arterioles (PE) measured at the first branching point of the peritubular capillaries (n = 5 rats/8 tubules) was 13.9 ± 0.5 mmHg. In the time control group (n = 4/8), these values were not significantly altered during the entire experiment (Fig. 4). However, intravenous infusion of 7-OH-DPAT (1.0 µg · kg-1 · min-1) significantly increased SFP (n = 5/8) up to 37.7 ± 0.8 mmHg (P < 0.001) and lowered PE (n = 5 rats/8 tubules) to 12.3 ± 0.4 mmHg (P < 0.003). MAP and HR remained unchanged during infusion of isotonic saline in the time control animals, whereas 7-OH-DPAT administration slightly decreased HR without affecting MAP (Table 3).


View larger version (17K):
[in this window]
[in a new window]
 
Fig. 4.   Effect of 7-OH-DPAT on stop-flow pressure (SFP; A) in early proximal tubules and on hydrostatic pressure in efferent arterioles (PE; B). BAS, baseline period (infusion of isotonic saline); EXP, experimental period (infusion of isotonic saline in time controls or 7-OH-DPAT). Data are means ± SE; n = 4 rats, 8 tubules or 8 star vessels in time control rats; n = 5/8/8 in 7-OH-DPAT group. * P < 0.05 vs. baseline period.


                              
View this table:
[in this window]
[in a new window]
 
Table 3.   Characteristics of micropuncture experiments


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Since the pioneering investigations by Goldberg et al. (for review, see Ref. 7), numerous functional studies on dopaminergic actions in the kidney have been carried out, mainly addressing the D1 and D2 receptor subtypes. However, the experiments revealed unequivocal results. For instance, the D2-like receptor agonist bromocriptine was reported to increase RBF and single nephron glomerular filtration rate (SNGFR) in anesthetized rats without affecting sodium excretion (21). Similarly, the D2-like receptor agonist quinpirole was demonstrated to increase SNGFR (15) and whole-kidney GFR in rats (10). In contrast, intrarenal administration of quinpirole in uninephrectomized conscious dogs reduced GFR and renal plasma flow (18). In a similar study, the D2 antagonist YM-09151 increased GFR, which was paralleled by a significant natriuresis and diuresis (17). These inconsistent observations on renal effects of dopamine D1 and D2 receptor activation may be due to differences in species and experimental settings or to insufficient selectivity of the pharmacological tools employed. Another reason might be that dopamine receptor subtypes other than D1 and D2 contribute to dopamine-induced changes in renal function. In this context, D3 receptors are increasingly gaining interest since Asico et al. (1) suggested that D3 receptors may play a role in renal and cardiovascular pathophysiology; transgenic mice lacking both alleles of the D3 receptor gene developed hypertension combined with an impaired ability to excrete an acute saline load. The D3 receptor, without doubt, is present in the kidney. Very recently, O'Connell et al. (4) demonstrated, by light microscopic immunohistochemistry, the localization of this receptor subtype in the proximal and distal tubules, glomeruli, and renal vasculature. Furthermore, electron microscopic immunocytochemistry revealed D3 receptor staining in the arteriolar smooth muscle cells of the renal vasculature and on the apical portions of the tubule cells. Pharmacological D3 receptor activation in normal Sprague-Dawley rats induced an increase in GFR and in urinary volume as well as sodium excretion (9).

In accordance with the latter observations, in the present experiments 7-OH-DPAT, a selective agonist of D3 receptors (2), increased GFR in a dose-dependent manner (Fig. 1). Arterial blood pressure was not altered, and a slight decrease in HR was observed in the different experimental groups, irrespective of changes in GFR and RBF. Therefore, an indirect effect of 7-OH-DPAT on renal hemodynamics, e.g., by influencing the systemic circulation, appears to be unlikely. To assess the contribution of D3 receptors to the 7-OH-DPAT-induced renal changes, RBF experiments were performed after pretreatment with either a D2 or a D3-receptor antagonist (SUL or U-99194A, respectively). It may be argued that SUL, as observed in vitro, possessed an only slightly greater binding affinity for D2 than D3 receptors (19) and therefore might not discriminate sufficiently between both receptor subtypes. However, in the present experiments, SUL at a dose sufficient to inhibit D2 receptors as confirmed previously in vivo (10) did not alter the renal effects of 7-OH-DPAT whereas inhibition of D3 receptors by U-99194A (23) completely abolished the renal effects of 7-OH-DPAT. Taken together, these data indicate that 7-OH-DPAT directly influences renal hemodynamics by selective activation of D3 receptors in the kidney.

The GFR response to 7-OH-DPAT was accompanied by a reduction in RBF and an elevated RVR. We hypothesized that this significant increase in FF might result from vasoconstriction of the postglomerular capillary. In an attempt to test the hypothesis of a postglomerular vasoconstriction in response to D3 receptor activation, micropuncture techniques were employed. SFP in early proximal tubules, taken as a surrogate of glomerular capillary pressure, was significantly increased by 7-OH-DPAT administration. In accordance with the hypothesis of a constriction of the efferent arteriole, the hydrostatic pressure in the first branching point of the efferent arteriole on the kidney surface was significantly reduced during 7-OH-DPAT infusion. Because a postglomerular vasoconstriction alone may not be sufficient to explain a decrease in RBF by 20%, the observed increase in RVR and fall in RBF in response to 7-OH-DPAT may result from vasoconstriction of both pre- and postglomerular vessels. The GFR increase despite a fall in RBF suggests, however, that vasoconstriction prevailed in post- over preglomerular vessels. The idea that additional factors may come into play to explain the increase in GFR, e.g., changes in contractile properties of mesangial cells, has to be addressed in further studies.

A postglomerular vasoconstriction by dopamine D3 receptor activation has not been described before. Numerous investigations demonstrated that exogenous dopamine, administered in low doses, increases RBF, which was ascribed by most authors to dopamine D1 and, to a lesser extent, to D2 receptor activation (for review, see Ref. 14). In the split hydronephrotic rat kidney, Steinhausen et al. (20) observed that locally applied dopamine dilated both the afferent and, to a lesser extent, the efferent arterioles; this effect was inhibited by haloperidol, a dopamine-receptor antagonist with a relatively low selectivity for the D2 subtype. At higher concentrations, dopamine also exerted vasoconstrictive effects, but these actions were most likely due to activation of alpha -adrenergic receptors. Another explanation for a 7-OH-DPAT-mediated postglomerular vasoconstriction might be an indirect effect, e.g., by induction of other vasoactive mediators such as angiotensin II. However, D3 receptor activation inhibits renin release from isolated juxtaglomerular cells (13). Therefore, a D3 receptor-induced release of angiotensin II appears to be less likely to account for the proposed efferent arteriolar vasoconstriction in response to 7-OH-DPAT.

In anesthetized rats quinpirole, a D2-like receptor agonist with a higher in vitro selectivity for D3 over D2 receptors (19), increased both RBF and GFR (15) whereas in conscious dogs intrarenal infusion of quinpirole caused a reduction in both renal parameters (18). These data appear to be rather inconsistent with the observation of a 7-OH-DPAT-induced hyperfiltration associated with a decrease in RBF. However, studies on the selectivity obtained in in vitro assays are not necessarily applicable to the data in in vivo studies. In addition, quinpirole has been described to be also a potent agonist at dopamine D4 receptors (22). Recently, the mRNA of this receptor has been demonstrated in the mammalian kidney (11), but the effects of D4 receptor activation on renal hemodynamics have not been investigated so far.

In summary, we demonstrate that D3 receptor activation in the normotensive anesthetized rat increases RVR asssociated with an elevation of GFR. Micropuncture experiments supported the hypothesis that an efferent vasoconstriction contributed to this GFR increase. Whether other factors are involved in the 7-OH-DPAT-induced effects on renal microcirculation has to be clarified by further investigations.


    ACKNOWLEDGEMENTS

We thank Christine Piesch and Kerstin Richter for excellent technical assistance.


    FOOTNOTES

This study was supported by the Federal Ministry of Education and Research and the Interdisciplinary Center for Clinical Research (IZKF Tübingen, 01 KS 9602) and by the Deutsche Forschungsgemeinschaft (Mu 1297/1-2).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Address for reprint requests and other correspondence: G. Luippold, Dept. of Pharmacology, Univ. of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany (E-mail: gerd.luippold{at}uni-tuebingen.de).

Received 21 December 1998; accepted in final form 24 November 1999.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Asico, LD, Ladines C, Fuchs S, Accili D, Carey RM, Semeraro C, Pocchiari F, Felder RA, Eisner GM, and Jose PA. Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension. J Clin Invest 102: 493-498, 1998[Abstract/Free Full Text].

2.   Baldessarini, RJ, Kula NS, McGrath CR, Bakthavachalam V, Kebabian JW, and Neumeyer JL. Isomeric selectivity at dopamine D3 receptors. Eur J Pharmacol 239: 269-270, 1993[ISI][Medline].

3.   O'Connell, DP, Botkin SJ, Ramos SI, Sibley DR, Ariano MA, Felder RA, and Carey RM. Localization of dopamine D1A receptor protein in rat kidney. Am J Physiol Renal Fluid Electrolyte Physiol 268: F1185-F1197, 1995[Abstract/Free Full Text].

4.   O'Connell, DP, Vaughan CJ, Aherne AM, Botkin SJ, Wang ZQ, Felder RA, and Carey RM. Expression of the dopamine D3 receptor protein in the rat kidney. Hypertension 32: 886-895, 1998[Abstract/Free Full Text].

5.   Felder, RA, Felder CC, Eisner GM, and Jose PA. The dopamine receptor in adult and maturing kidney. Am J Physiol Renal Fluid Electrolyte Physiol 257: F315-F328, 1989[Abstract/Free Full Text].

6.   Gao, D-Q, Canessa LM, Mouradian MM, and Jose PA. Expression of the D2 subfamily of dopamine receptor genes in kidney. Am J Physiol Renal Fluid Electrolyte Physiol 266: F646-F650, 1994[Abstract/Free Full Text].

7.   Goldberg, LI. Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev 24: 1-29, 1972[ISI][Medline].

8.   Hansell, P, and Fasching A. The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia. Kidney Int 39: 253-258, 1991[ISI][Medline].

9.   Luippold, G, Küster E, Joos TO, and Mühlbauer B. Dopamine D3 receptor activation modulates renal function in anesthetized rats. Naunyn Schmiedeberg's Arch Pharmacol 358: 690-693, 1998[ISI][Medline].

10.   Luippold, G, and Mühlbauer B. Dopamine D2-receptors mediate glomerular hyperfiltration due to amino acids. J Pharmacol Exp Ther 286: 1248-1252, 1998[Abstract/Free Full Text].

11.   Matsumoto, M, Hidaka K, Tada S, Tasaki Y, and Yamaguchi T. Full-length cDNA cloning and distribution of human dopamine D4 receptor. Mol Brain Res 29: 157-162, 1995[ISI][Medline].

12.   Nash, SR, Godinot N, and Caron MG. Cloning and characterization of the opossum kidney cell D1 dopamine receptor: expression of identical D1A and D1B dopamine receptor mRNAs in opossum kidney and brain. Mol Pharmacol 44: 918-925, 1993[Abstract].

13.   Sanada, H, Yao L, Jose PA, Carey RM, and Felder RA. Dopamine D3 receptors in rat juxtaglomerular cells. Clin Exp Hypertens 19: 93-105, 1997[ISI][Medline].

14.   Schwartz, LB, and Gewertz BL. The renal response to low dose dopamine. J Surg Res 45: 574-588, 1988[ISI][Medline].

15.   Seri, I, and Aperia A. Contribution of dopamine2 receptors to dopamine-induced increase in glomerular filtration rate. Am J Physiol Renal Fluid Electrolyte Physiol 254: F196-F201, 1988[Abstract/Free Full Text].

16.   Sibley, DR, and Monsma FJ. Molecular biology of dopamine receptors. Trends Pharmacol Sci 13: 61-69, 1992[ISI][Medline].

17.   Siragy, HM, Felder RA, Howell NL, Chevalier RL, Peach MJ, and Carey RM. Evidence that dopamine-2 mechanisms control renal function. Am J Physiol Renal Fluid Electrolyte Physiol 259: F793-F800, 1990[Abstract/Free Full Text].

18.   Siragy, HM, Felder RA, Peach MJ, and Carey RM. Intrarenal DA2 dopamine receptor stimulation in the conscious dog. Am J Physiol Renal Fluid Electrolyte Physiol 262: F932-F938, 1992[Abstract/Free Full Text].

19.   Sokoloff, P, Andrieux M, Besancon R, Pilon C, Martres MP, Giros B, and Schwartz JC. Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol 225: 331-337, 1992[Medline].

20.   Steinhausen, M, Weis S, Fleming J, Dussel R, and Parekh N. Responses of in vivo renal microvessels to dopamine. Kidney Int 30: 361-370, 1986[ISI][Medline].

21.   Stier, CT, Jr, Cowden EA, and Allison ME. Effects of bromocriptine on single nephron and whole-kidney function in rats. J Pharmacol Exp Ther 220: 366-370, 1982[Abstract].

22.   Tang, L, Todd RD, Heller A, and O'Malley KL. Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines. J Pharmacol Exp Ther 268: 495-502, 1994[Abstract].

23.   Waters, N, Svensson K, Haadsma-Svensson SR, Smith MW, and Carlsson A. The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity. J Neural Transm Gen Sect 94: 11-19, 1993[Medline].


Am J Physiol Renal Fluid Electrolyte Physiol 278(4):F570-F575
0363-6127/00 $5.00 Copyright © 2000 the American Physiological Society