Dopamine inhibits Na(+)-H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase

Abstract

To determine a renal tubular mechanism for the natriuretic effect of dopamine (DA) and DA-1 agonists, we measured Na(+)-H+ exchange activity (amiloride sensitive) in rat renal cortical brush-border membrane vesicles (BBMV). Renal cortical tissues were preincubated with ligands before BBMV preparation to study Na(+)-H+ exchange activity in the absence of the added ligands that may compete for ion binding sites of the exchanger. DA and DA-1 agonist-inhibited Na(+)-H+ exchange activity was concentration and time dependent. The inhibitory effect was not due to increased permeability, collapse of the proton gradient, or change in vesicle size and did not extend to Na(+)-glucose symport. DA-2 agonists had no effect, whereas alpha-adrenergic agonists increased Na(+)-H+ exchange activity. Kinetic analysis revealed that the DA-1 agonist inhibited Na(+)-H+ exchange activity by a noncompetitive process. 2',5'-Dideoxyadenosine inhibited adenylate cyclase activity and reversed the inhibitory effect of DA-1 agonist on the exchanger. H4, an isoquinoline sulfonamide, which inhibits protein kinase A, also reversed the inhibitory effect of DA-1 agonist on the exchanger. Thus the DA-1 agonist-mediated inhibition of Na(+)-H+ exchange activity in BBMV is a receptor-mediated adenylate cyclase-linked process.

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

“…It has been previously reported that H89 fully or partially prevented the NHE inhibition induced by 8-Br-cAMP or by factors that increase intracellular cAMP levels (5,(26)(27)(28)(29). Therefore, we analyzed the effect of H89 on the PKA-and EPAC-dependent inhibitions.…”

Dopamine, hypertension and obesity

“…20,29,30 Modulation mechanisms of the response to DA Na + /H + exchanger It is inhibited by the paracrine effect of DA on the proximal tube resulting from D 1 receptors activation, which stimulates adenyl cyclase. 31 However, it can be also inhibited by a mechanism independent of the cAMP generation, directly through the G protein interaction. 32 Another inhibiting mechanism independent of cAMP is that taking place through PLC activation.…”

Aging, High Salt Intake, and Renal Dopaminergic Activity in Fischer 344 Rats

“…1,2 At the level of the proximal tubule, the overall increase in sodium excretion produced by dopamine and D 1 receptor agonists results from inhibition of Na ϩ ,K ϩ -adenosine triphosphatase (Na ϩ ,K ϩ -ATPase) 3 and the Na ϩ /H ϩ exchanger. 4 Inhibition of Na ϩ ,K ϩ -ATPase by dopamine occurs via a phospholipase C-coupled protein kinase C-linked pathway. 5,6 Stimulation of D 1 receptors leads to inhibition of the Na ϩ /H ϩ exchanger as a result of increased adenosine 3Ј,5Јcy-clic monophosphate formation and subsequently via protein kinase A-mediated phosphorylation.…”