Characterization of receptors involved in dopamine-induced activation of phospholipase-C in rat renal cortex.
Dopamine (DA) is reported to stimulate phospholipase-C (PL-C) in rat renal cortex. Inasmuch as DA activates alpha adrenoceptors and DA receptors, the relative contribution of these receptors to DA-induced activation of PL-C is not yet established. We examined the effect of DA on PL-C activity in rat renal cortical slices prelabeled with myo-2-[3H]inositol in the presence of Li+. PL-C activity was expressed as fractional release (FR) of combined [3H]inositol phosphates expressed as dpm inositol phosphates accumulated/total dpm incorporated X 100. DA (1 mM) produced time-dependent increases in FR up to 60 min. DA (1, 3 and 10 mM) produced 61%, 88% and 110% increases in FR over control. When DA was given in the presence of SCH 23390, a selective DA-1 receptor antagonist, the increase in FR was significantly reduced to 33%, 51% and 62%, respectively, but the increase in FR remained unaffected in the presence of a DA-2 receptor antagonist, domperidone (30 microM). Phentolamine (10 microM) also inhibited the response to DA to 41%, 47% and 43% at the respective concentrations. DA-induced stimulation of PL-C was completely abolished in the combined presence of both SCH 23390 (30 microM) and phentolamine (10 microM). SCH 23390, domperidone or phentolamine alone did not significantly change the basal PL-C activity in renal cortical slices. These results demonstrate that 1) DA stimulates PL-C in rat renal cortex via activation of both DA-1 receptors and alpha adrenoceptors and DA-2 receptors are not involved in this response; and 2) during normal sodium intake, intrarenal DA does not modulate the PL-C activity in rat renal cortex.
Department of Pharmacology, University of Houston, Texas.
S J
SJ
Vyas
J
J
Eichberg
M F
MF
Lokhandwala
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D011954:Receptors, Dopamine; D010738:Type C Phospholipases; D004298:Dopamine