ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1987.tb04118.x
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