Diminished phospholipase C activation by dopamine in spontaneously hypertensive rats.
It is reported that a defect in dopamine-1 (DA-1) receptor adenylate cyclase coupling in the proximal convoluted tubule in the spontaneously hypertensive rat may contribute to the diminished natriuretic response to DA-1 receptor agonists. Since the tubular DA-1 receptor is also coupled to phospholipase C, and both of these cellular signaling processes are involved in DA-1 receptor-mediated diuresis and natriuresis, it is important to know whether a similar defect is also present in DA-1 receptor-coupled phospholipase C pathway. The present study was therefore designed to determine the functional status of DA-1 receptor-phospholipase C coupling system of adult spontaneously hypertensive rats using a renal cortical slice preparation. In addition, the renal response to exogenously administered dopamine (1 microgram/kg/min i.v.) was also determined. We found that basal phospholipase C activity was significantly higher in hypertensive rats than in age-matched Wistar-Kyoto rats (7.36 +/- 0.32% versus 5.61 +/- 0.27%, p less than 0.05). However, compared with the normotensive controls, dopamine-induced increases in phospholipase C activity were significantly attenuated in the preparations of hypertensive rats in a concentration-dependent manner (13 +/- 6% versus 38 +/- 6% for 1 mM dopamine, p less than 0.05; 49 +/- 6% versus 71 +/- 9% for 3 mM dopamine, p less than 0.05; 50 +/- 16% versus 106 +/- 22%, p less than 0.05 for 10 mM dopamine).(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
C J
CJ
Department of Pharmacology, University of Houston, Tex. 77204-5515.
Vyas
S J
SJ
Eichberg
J
J
Lokhandwala
M F
MF
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
D001552:Benzazepines; D007295:Inositol Phosphates; D010738:Type C Phospholipases; D004298:Dopamine; D010646:Phentolamine