Transmembrane signalling of atrial natriuretic peptide in rat renal juxtaglomerular cells.
Recently we have shown that atrial natriuretic peptide (ANP) inhibits renin release from isolated rat renal juxtaglomerular (JG) cells. ANP in general is thought to act on its target cells by the binding to specific membrane receptors. It is the objective of this contribution to summarize our present knowledge about the sequence of events by which the occupancy of ANP receptors could lead to an inhibition of renin release from juxtaglomerular (JG) cells. It was found that ANP did not affect the intracellular concentration of calcium. ANP led to a dose dependent increase in the intracellular concentration of cyclic GMP and to a dose dependent decrease of cAMPi. Inhibition of renin release from the JG-cells by ANP was clearly correlated to the level of cGMPi and not to the level of cAMPi. Concerning the mechanism by which ANP causes a rise in cGMPi in JG-cells it was found that the effect of ANP on cGMPi was potentiated by the cGMP phosphodiesterase specific inhibitor M & B 22,948. This finding suggests that ANP enhances cGMPi by the stimulation of a guanylate cyclase rather than by the inhibition of a cGMP phosphodiesterase. Moreover, evidence was obtained that the effect of ANP on cGMP, was markedly attenuated after pretreatment of the JG-cells with pertussis toxin. Since pertussis toxin is considered to inactivate guanine nucleotide binding proteins (G-proteins), this result could indicate that ANP receptors are coupled to a guanylate cyclase via a G-protein. Experimental evidence suggests that the G-protein in question might be the inhibitory unit (Ni) of the adenylate cyclase.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000502:physiology; D012083:Renin / Q000378:metabolism
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D012083:Renin; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP