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https://hdl.handle.net/10316/3901
Título: | Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels | Autor: | Sena, Cristina M. Santos, Rosa M. Boarder, Michael R. Rosário, Luís M. |
Palavras-chave: | Adrenal medulla chromaffin cell; Ca2+ concentration, cytosolic free; Phorbol ester; Protein kinase C; Ca2+ channel, voltage-sensitive | Data: | 1999 | Citação: | European Journal of Pharmacology. 366:2-3 (1999) 281-292 | Resumo: | Phorbol esters reduce depolarization-evoked Ca2+ influx in adrenal chromaffin cells, suggesting that voltage-sensitive Ca2+ channels (VSCCs) are inhibited by protein kinase C-mediated phosphorylation. We now address the possibility that L- and P/Q-type Ca2+ channel subtypes might be differentially involved in phorbol ester action. In bovine chromaffin cells, short-term (10 min) incubations with phorbol 12-myristate 13-acetate (PMA) inhibited early high K+-evoked rises in cytosolic free Ca2+ concentration ([Ca2+]i) and the early component of the depolarization-evoked Mn2+ quenching of fura-2 fluorescence in a dose-dependent manner (IC50: 18 and 7 nM; maximal inhibitions: 45 and 48%, respectively). The protein kinase C inhibitor staurosporine (100 nM) reverted the inhibitory action of PMA. PMA (0.1-1 [mu]M) inhibited the early and late phases of the ionomycin (2 [mu]M)-evoked [Ca2+]i transients by 14-23%. [omega]-Agatoxin IVA, a blocker of P/Q-type Ca2+ channels, inhibited high K+-evoked [Ca2+]i rises in a dose-dependent fashion (IC50=50 nM). In contrast, 0.1 [mu]M [omega]-conotoxin GVIA, a blocker of N-type channels, was without effect. A sizeable (<45%) component of early Ca2+ influx persisted in the combined presence of [omega]-agatoxin IVA (100 nM) and nitrendipine (1 [mu]M). Simultaneous exposure to [omega]-agatoxin IVA and PMA inhibited both the early [Ca2+]i transients and Mn2+ quenching to a much greater extent than each drug separately. Inhibition of the [Ca2+]i transients by nitrendipine and PMA did not significantly exceed that produced by PMA alone. It is concluded that phorbol ester-mediated activation of protein kinase C inhibits preferentially L-type VSCCs over P/Q type channels in adrenal chromaffin cells. However, the possibility cannot be ruled out that dihydropyridine-resistant, non-P/Q type channels might also be negatively regulated by protein kinase C. This may represent an important pathway for the specific control of VSCCs by protein kinase C-linked receptors, not only in paraneurones but presumably also in neurones and other excitable cells. | URI: | https://hdl.handle.net/10316/3901 | DOI: | 10.1016/S0014-2999(98)00908-X | Direitos: | openAccess |
Aparece nas coleções: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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fileb49cc84bfa374c2f8701db3f424e8e29.pdf | 390.33 kB | Adobe PDF | Ver/Abrir |
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