Two components in the adrenal nicotinic secretory response revealed by cobalt ramps

Abstract

Prolonged stimulation with nicotine (50 μM) enhanced the secretion of catecholamines from perfused cat adrenal glands. The profile of secretion consisted of a quick activation phase to peak of 7.68 μg/min followed by a second inactivation phase which exhibited a t 1 2 of 3.75 min. Sustained stimulation with a solution enriched in K + (59 mM) also evoked a transient secretory response, with a peak release of 8.62 μg/2 min and a t 1 2 for inactivation of 4.8 min. Co 2+ (10 mM) blocked the nicotinic response by 58% and the K +-evoked secretory response by over 96%. In the presence of Co 2+; (5 mM), continuous perfusion with nicotine produced a transient but large initial secretory response; the gradual decrease of the extracellular Co 2+ concentration, [Co 2+] 0, as a continuous ramp allowed the development of a second component of secretion which inactivated later on. When the glands were continuously stimulated with 59 mM K + in the presence of Co 2+, the first component of secretion was missing: the second component appeared as [Co 2+] 0 decreases as a ramp. In similar experiments performed in low-Na + solution (10 mM Na +), only the first secretion component evoked by nicotine was observed. This finding suggests that the second component of secretion depends on Na + entry through the nicotinic receptor, on the ensuing cell depolarization and on Ca 2+ entry through voltage-dependent Ca 2+ channels. These data are compatible with the idea that the nicotinic receptor-mediated catecholamine secretory response in the cat adrenal chromaffin cell has two components: the first seem to be triggered by Ca 2+ entry through the nicotinic receptor channels, and the second by Ca 2+ entry through voltage-dependent Ca 2+ channels. The data also suggest that Co 2+ ions protect against the Ca 2+-dependent desensitization of nicotinic receptors.