Dopamine D1 Receptor Regulation of Phospholipase C

Abstract

Dopamine is an endogenous catecholamine which exerts its actions by occupancy of specific receptors. Dopamine receptors are classified into two main groups: the two cloned D1-like receptors (D1A and D1B in rats; D1B is also known as D5 in humans) are linked to stimulation of adenylyl cyclase, while the three cloned D2-like receptors (D2 or D2A D3 or D2B D4 or D2C) are linked to inhibition of adenylyl cyclase. All these dopamine receptors originally cloned from the brain are expressed in tissues outside the central nervous system including the kidney. Dopamine regulates many cellular activities, including transmembrane ion transport. Activation of D1-like receptor decreases sodium transport by cAMP dependent and cAMP independent mechanisms. Dopamine, via D1-like receptors, may inhibit Na+/H+ exchange activity in renal brush border membranes by a cAMP independent/Gsα-linked mechanism. Another cAMP independent pathway of sodium transport inhibition is mediated by phospholipase C, which has several isoforms (PLC β, PLC γ, and PLC δ with several members in each). Catecholamines stimulate expression and activity of phospholipase C isoforms in a concentration, time, and receptor-dependent as well as regional and subcellular compartmental-specific manner. In renal cortical membranes, intrarenal administration of norepinephrine for 3-4 h increases PLC β1 expression and activity but has no effect on PLC δ activity. In contrast, intrarenal administration of a Di agonist for 3-4 h increases PLC/#i but decreases PLC/ expression and activity. In membranes from LTK- cells transfected with the rat D1A receptor cDNA, D1 receptor stimulation initially increases and then in 4 h decreases PLC δ expression and activity, similar to the results found in renal cortical membranes. The initial increase of PLC δ expression and activity due to Dx receptors is mediated by protein kinase A. (Hypertens Res 1995; 18 Suppl. I: S39S42). © 1995, The Japanese Society of Hypertension. All rights reserved.