C-type natriuretic peptide neuromodulates independently of guanylyl cyclase activation.
Of the four endogenous members of the natriuretic peptide family, only atrial natriuretic peptide has been demonstrated to have neuromodulatory effects. This study compares the neuromodulatory effects of atrial natriuretic peptide and a recently identified natriuretic peptide, C-type natriuretic peptide, in the rabbit isolated vas deferens. The ability of these peptides to alter cyclic nucleotide concentrations was assessed to determine the potential contribution of either cyclic AMP or cyclic GMP to the observed responses. The central hypothesis tested was that C-type natriuretic peptide modulates neurotransmission via an interaction with a guanylyl cyclase. C-type natriuretic peptide inhibited both purinergic and adrenergic neurotransmission in a concentration-dependent manner but failed to alter either cyclic GMP or cyclic AMP concentrations. Maximal inhibitory effects of C-type natriuretic peptide averaged 35 +/- 4% for purinergic and 49 +/- 7% for adrenergic neurotransmission. Atrial natriuretic peptide not only attenuated both purinergic and adrenergic neurotransmission but also increased cyclic GMP concentrations. C-type natriuretic peptide probably inhibited the release of the neurotransmitters because it failed to alter contractions to exogenously administered norepinephrine or ATP, the two putative neurotransmitters. These results suggest that the C-type natriuretic peptide receptor, guanylyl cyclase B, is not present in rabbit vas deferens and that C-type natriuretic peptide suppresses peripheral sympathetic neurotransmission independently of guanylyl cyclase activation.
Trachte
G J
GJ
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine 55812.
Drewett
J G
JG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010566:Virulence Factors, Bordetella; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP