Attenuation of adenylate cyclase-induced increases in renal sodium excretion by the dopamine D-2 receptor agonist SK&F 89124.
1. Although the existence of D-2 receptor binding sites in kidney has been identified, their functional significance in terms of influencing renal sodium excretion is not clear. In the present study we have examined the renal effects of a selective D-2 receptor agonist, SK&F 89124, in anaesthetized rats. 2. Intravenous infusion of SK&F 89124 (0.3, 1 and 3 micrograms kg-1 min-1 respectively) produced dose-dependent decreases in mean arterial blood pressure, heart rate and renal blood flow without causing any significant changes in urine output, urinary sodium excretion, renal vascular resistance or glomerular filtration rate. The changes in blood pressure, heart rate and renal blood flow caused by SK&F 89124 were abolished by a selective D-2 receptor antagonist, domperidone (50 micrograms kg-1 i.v. bolus; 10 micrograms kg-1 min-1). 3; Treatment with 3-isobutyl-1-methylxanthine (IBMX, 1 mg kg-1 bolus i.v.) or forskolin (200 micrograms kg-1 bolus i.v.) produced increases in heart rate, urine output and urinary sodium excretion, but there was no change in mean blood pressure. The natriuretic and diuretic response, but not tachycardiac response to IBMX or forskolin, was attenuated by SK&F 89124 (0.3 micrograms kg-1 min-1). 4. These results suggest that the selective D-2 receptor agonist, SK&F 89124, produced a significant decrease in blood pressure and heart rate via prejunctional D-2 receptor-mediated inhibition of noradrenaline release from postganglionic sympathetic nerve terminals. Although activation of renal tubular D-2 receptors had no significant effect on renal excretory function under basal conditions, it is likely that these receptors may exert an opposing effect on cAMP-mediated increases in renal sodium and water excretion.
Sakamoto
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T
Department of Pharmacology, University of Houston, TX 77024-5515.
Chen
C
C
Lokhandwala
M F
MF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012964:Sodium / Q000378:metabolism*
D007211:Indoles; D017448:Receptors, Dopamine D2; D005576:Colforsin; D004294:Domperidone; C047183:SK&F 89124; D012964:Sodium; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine