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Inhibition of voltage-dependent Ca2+ channels via alpha 2-adrenergic and opioid receptors in cultured bovine adrenal chromaffin cells

Item Type:Article
Title:Inhibition of voltage-dependent Ca2+ channels via alpha 2-adrenergic and opioid receptors in cultured bovine adrenal chromaffin cells
Creators Name:Kleppisch, T. and Ahnert-Hilger, G. and Gollasch, M. and Spicher, K. and Hescheler, J. and Schultz, G. and Rosenthal, W.
Abstract:Adrenal chromaffin cells secrete catecholamines and opioids. The effects of these agents on whole-cell Ca2+ channel currents were studied, using bovine adrenal chromaffin cells kept in short term culture. Ca2+ channel currents recorded during voltage-clamp pulses from a holding potential of -80 mV to 0 mV were reversibly reduced by 10 microM epinephrine (in the presence of 1 microM propranolol) or 5 microM of the synthetic opioid, d-Ala2-d-Leu5-enkephalin (DADLE) by approximately 35% and 25%, respectively. The inhibitory action of epinephrine was mimicked by clonidine, reduced by yohimbine but not affected by prazosin. The DADLE-induced reduction of the Ca2+ channel current was antagonized by naloxone. The dihydropyridine (+)PN 200-110 (5 microM) reduced the Ca2+ channel current by approximately 40%; the Ca2+ channel current inhibited by (+)PN 200-110 was not further reduced by epinephrine. Intracellular infusion of guanosine-5'-O-(2-thiodiphosphate) and pretreatment of cells with pertussis toxin abolished the inhibitory effect of both epinephrine and DADLE. In membranes of adrenal chromaffin cells, four pertussis-toxin-sensitive G-proteins were identified, including Gi1, Gi2, Go1 and another Go subtype, possibly Go2. The data show that activation of alpha 2-adrenergic and opioid receptors causes an inhibition of dihydropyridine-sensitive Ca2+ channels in adrenal chromaffin cells. These inhibitory modulations are mediated by pertussis-toxin-sensitive G-proteins and may represent a mechanism for a negative feedback signal by agents released from the adrenal medulla.
Keywords:Adrenal Chromaffin Cell, Voltage-Dependent Ca2+ Channels, agr2-Adrenoceptors, Opioid Receptors, G-Proteins, Patch-Clamp, Animals, Cattle
Source:Pfluegers Archiv European Journal of Physiology
ISSN:0031-6768
Publisher:Springer (Germany)
Volume:421
Number:2-3
Page Range:131-137
Date:June 1992
Official Publication:https://doi.org/10.1007/BF00374819
PubMed:View item in PubMed

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