C-type natriuretic peptide neuromodulates via 'clearance' receptors

George J Trachte, S. Kanwal, B. J. Elmquist, R. J. Ziegler

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38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)C978-C984
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 37-4
StatePublished - 1995


  • adenosine 3',5'-cyclic monophosphate
  • clearance receptors
  • guanosine 3',5'-cyclic monophosphate
  • guanylyl cyclase
  • natriuretic peptides
  • neuromodulators


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