PT  - JOURNAL ARTICLE
AU  - S. Kanwal
AU  - B. J. Elmquist
AU  - G. J. Trachte
TI  - Atrial Natriuretic Peptide Inhibits Evoked Catecholamine Release by Altering Sensitivity to Calcium
DP  - 1997 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 426--433
VI  - 283
IP  - 2
4099  - http://jpet.aspetjournals.org/content/283/2/426.short
4100  - http://jpet.aspetjournals.org/content/283/2/426.full
SO  - J Pharmacol Exp Ther1997 Nov 01; 283
AB  - Natriuretic peptides are cyclized peptides produced by cardiovascular and neural tissues. These peptides inhibit various secretory responses such as the release of renin, aldosterone and autonomic neurotransmitters. This report tests the hypothesis that atrial natriuretic peptide reduces dopamine efflux from an adrenergic cell line, rat pheochromocytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dopamine release from depolarized PC12 cells, suggesting that calcium entering through this channel was the predominant stimulus for dopamine efflux. Atrial natriuretic peptide maximally reduced depolarization-evoked dopamine release 20 ± 3% at a concentration of 100 nM and this effect was abolished by nifedipine, but not by pretreatment with the N-type calcium channel inhibitor, ω-conotoxin, or an inhibitor of calcium-induced calcium release, ryanodine. In cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced increases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, findings consistent with enhanced conductivity of calcium channels. Dopamine efflux induced by either the calcium ionophore, A23187, or staphylococcal α toxin was attenuated by atrial natriuretic peptide. Additionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also suppressed calcium-induced dopamine efflux in permeabilized cells. These data are consistent with natriuretic peptides attenuating catecholamine exocytosis in response to calcium but inconsistent with the neuromodulatory effect resulting from a reduction in intracellular calcium concentrations within pheochromocytoma cells. The American Society for Pharmacology and Experimental Therapeutics