ATRIAL-NATRIURETIC-PEPTIDE INHIBITS EVOKED CATECHOLAMINE RELEASE BY ALTERING SENSITIVITY TO CALCIUM

Natriuretic peptides are cyclized peptides produced by cardio-vascular and neural tissues. These peptides inhibit various secretory response s such as the release of renin, aldosterone and autonomic neurotransmi tters. This report tests the hypothesis that atrial natriuretic peptid e reduces dopamine efflux from an adrenergic cell line, rat pheochromo cytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dop amine release from depolarized PC12 cells, suggesting that calcium ent ering through this channel was the predominant stimulus for dopamine e fflux. Atrial natriuretic peptide maximally reduced depolarization-evo ked dopamine release 20 +/- 3% at a concentration of 100 nM and this e ffect was abolished by nifedipine, but not by pretreatment with the N- type calcium channel inhibitor, omega-conotoxin, or an inhibitor of ca lcium-induced calcium release, ryanodine. in cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced incr eases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, f indings consistent with enhanced conductivity of calcium channels. Dop amine efflux induced by either the calcium ionophore, A23187, or staph ylococcal ct toxin was attenuated by atrial natriuretic peptide. Addit ionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also s uppressed calcium-induced dopamine efflux in permeabilized cells. Thes e data are consistent with natriuretic peptides attenuating catecholam ine exocytosis in response to calcium but inconsistent with the neurom odulatory effect resulting from a reduction in intracellular calcium c oncentrations within pheochromocytoma cells.