C-type natriuretic peptide neuromodulates via "clearance" receptors. Trachte, George J., S. Kanwal, Barbara J. Elmquist, and Richard J. Ziegler. Departments of Pharmacology and Medical Microbiology and Immunology, University of Minnesota-Duluth, School of Medicine, Duluth, MN 55812, (218) -726-8975, FAX (218)-726-6235
APStracts 2:0031C, 1995.
A recently discovered endogenous autacoid, C-type natriuretic peptide, was tested in a pheochromocytoma (PC12) cell line for effects on: 1) catecholamine release induced by a depolarizing stimulus, 2) guanylyl and adenylyl cyclase activities, and 3) specific 125I-atrial natriuretic peptide binding. C-type natriuretic peptide suppressed evoked neurotransmitter release in the absence of guanylyl cyclase activation or adenylyl cyclase inhibition; however, both a &QUOTclearance&QUOT (ANP-C) receptor binding agent, cANF, and pertussis toxin prevented this neuromodulatory effect. The C-type natriuretic peptide preferentially bound to receptors that also bound cANF. The results suggest that C-type natriuretic peptide suppressed evoked neurotransmitter efflux by binding to ANP-C receptors coupled to a pertussis toxin-sensitive process; furthermore, the neuromodulatory effect of C-type natriuretic peptide occurred independently of guanylyl cyclase activation or adenylyl cyclase inhibition. The novel aspects of these findings are: 1) neuromodulatory effects of C-type natriuretic peptide; 2) guanylyl cyclase -independent actions of C-type natriuretic peptide; and 3) ANP-C receptors mediating C-type natriuretic peptide actions.

Received 15 March 1994; accepted in final form 15 November 1994
APS Manuscript Number C0144-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.