Intracellular fragments of the natriuretic peptide receptor-C (NPR-C) attenuate dopamine efflux

Natriuretic peptides suppress adrenergic neurotransmission by a mechanism a pparently involving the natriuretic peptide receptor-C (NPR-C) rather than particulate guanylyl cyclase receptors. The bulk of evidence implicating th e NPR-C in neuromodulatory effects relies on the pharmacological specificit y of peptides believed to be specific for the NPR-C. This study tests for N PR-C effects on neurotransmitter release by examining fragments of the rece ptor for biological activity in pheochromocytoma (PC12) cells permeabilized with digitonin. A pentadecapeptide segment of the cytoplasmic portion of t he NPR-C mimicked the effect of natriuretic peptides to suppress dopamine e fflux evoked by calcium approximately 40%. Furthermore, an antibody generat ed against the pentadecapeptide fragment abolished the neuromodulatory effe ct of C-type natriuretic peptide in permeabilized cells. In contrast, the c arboxy terminal nonadecapeptide portion of the NPR-C failed to attenuate do pamine efflux. These data are consistent with the proposed role of the NPR- C in transducing the biological activity of natriuretic peptides in adrener gic tissue. The most novel aspect of these observations involves the potenc y of the small cytosolic region of the NPR-C with the region closest to the membrane accounting for neuromodulatory effects.