Neuromodulatory effects of atrial natriuretic peptides correlate with an inhibition of adenylate cyclase but not an activation of guanylate cyclase

J. G. Drewett, R. J. Ziegler, George J Trachte

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

We reported previously that atrial natriuretic factor (ANF) and the ANF clearance receptor binding peptide, C-ANF(4-23)-NH2 C-ANF), inhibit catecholamine (CA) release from rat, nerve growth factor-treated pheochromocytoma cells (PC12 cells) by a guanylate cyclase independent mechanism. This mechanism is most likely a pertussis toxin (PTX)-sensitive inhibition of adenylate cyclase. This study examines the role of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), in mediating atrial natriuretic factor effects on depolarization-induced CA release from PC12 cells. The following evidence supports the hypothesis that the neuromodulatory action of atrial peptides is independent of increases in cGMP: 1) ANF does not potentiate the inhibitory effect of C-ANF on CA release or cAMP generation but still elevates cGMP concentrations in the presence of C-ANF; 2) the neuromodulatory effects of ANF and C-ANF are blocked or reversed by a membrane permeable analog of cAMP, dibutyryl cAMP; 3) ANF and C-ANF attenuate CA release in the presence of a maximally effective concentration of dibutyryl cGMP; 4) the inhibitory effect of dibutyryl cGMP is PTX-insensitive whereas the atrial peptide effect is blocked by PTX- pretreatment; and 5) dibutyryl cGMP is without effect on adenylate cyclase. These data are consistent with the hypothesis that ANF and C-ANF act via the ANF clearance (R2) receptor to suppress adenylate cyclase activity and neurotransmission.

Original languageEnglish (US)
Pages (from-to)689-696
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume260
Issue number2
StatePublished - 1992

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