Dihydropyridine Modulation of the Chromaffin Cell Secretory Response

Publisher Website
Google Scholar
Abstract
Prolonged perfusion of cat adrenal glands with Krebs‐bicarbonate solutions containing nicotine, musca‐rine, or excess K rapidly increased the rate of catecholamine output proportional to the concentrations of secretagogue used. The secretory responses to nicotine or high K reached a peak and declined to almost basal rates of secretion after about 10 min of stimulation. The dihydropyridine Ca channel agonist Bay K 8644 potentiated markedly the secretory responses to 1 μM nicotine and to 17.7 mM K but not to higher concentrations of these secretagogues. The musca‐rinic response did not decrease with time and was modestly potentiated by Bay K 8644. Similar curves were obtained with 17.7 mM K plus Bay K 8644 and with 59 mMK alone. CGP28392, another agonist, was about 10 times less potent than Bay K 8644 in potentiating the secretory responses to 17.7 mM K. Bay K 8644 also potentiated the release of I3H]noradrenaline evoked by stimulation of cultured bovine adrenal chromaffin cells with 17.7 mMK or 2μM nicotine but not with higher concentrations of K or nicotine. Dihydropyridine Ca channel antagonists reversed the effects of Bay K 8644 with the following order of potency: niludi‐pine ≥ nifedipine = nimodipine ≥ nitrendipine. The secretory rates from intact chromaffin cells treated with the Ca ionophores X537A or A23187, or those evoked by Ca‐EGTA buffers from digitonin‐permeabilized cells, were not affected by Bay K 8644. These results are compatible with the following conclusions: (1) Bay K 8644 selectively potentiates catecholamine secretory responses mediated through the activation of voltage‐sensitive Ca channels; (2) during nicotine or high‐K stimulation, Ca gains access to the cell interior through a common permeability pathway, the Ca channel; and (3) dihydropyridine Ca agonists and antagonists act on a common site on the chromaffin cell plasma membrane, perhaps a dihydropyridine receptor near the voltage‐dependent Ca channel and regulating it.

This publication has 19 references indexed in Scilit: