title: C-type natriuretic peptide neuromodulates via "clearance" receptors.
abstract: 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-labeled atrial natriuretic peptide (ANP) binding. C-type natriuretic peptide suppressed evoked neurotransmitter release in the absence of guanylyl cyclase activation or adenylyl cyclase inhibition; however, both a "clearance" (ANP-C) receptor binding agent, des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (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.
authors.affiliation: Department of Pharmacology, University of Minnesota-Duluth, School of Medicine 55812, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Trachte
authors.forename: S
authors.initials: S
authors.lastname: Kanwal
authors.forename: B J
authors.initials: BJ
authors.lastname: Elmquist
authors.forename: R J
authors.initials: RJ
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
chemical_list: C080026:C-type natriuretic peptide (1-22), Tyr(0)-; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D009712:Nucleotides, Cyclic; D010446:Peptide Fragments; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor