Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/3901
DC Field | Value | Language |
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dc.contributor.author | Sena, Cristina M. | - |
dc.contributor.author | Santos, Rosa M. | - |
dc.contributor.author | Boarder, Michael R. | - |
dc.contributor.author | Rosário, Luís M. | - |
dc.date.accessioned | 2008-08-29T15:35:52Z | - |
dc.date.available | 2008-08-29T15:35:52Z | - |
dc.date.issued | 1999 | en_US |
dc.identifier.citation | European Journal of Pharmacology. 366:2-3 (1999) 281-292 | en_US |
dc.identifier.uri | https://hdl.handle.net/10316/3901 | - |
dc.description.abstract | 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. | en_US |
dc.description.uri | http://www.sciencedirect.com/science/article/B6T1J-3VS1R39-N/1/a4fedd4ab766a663b3e97ea0cbd8f965 | en_US |
dc.format.mimetype | aplication/PDF | en |
dc.language.iso | eng | eng |
dc.rights | openAccess | eng |
dc.subject | Adrenal medulla chromaffin cell | en_US |
dc.subject | Ca2+ concentration, cytosolic free | en_US |
dc.subject | Phorbol ester | en_US |
dc.subject | Protein kinase C | en_US |
dc.subject | Ca2+ channel, voltage-sensitive | en_US |
dc.title | Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels | en_US |
dc.type | article | en_US |
dc.identifier.doi | 10.1016/S0014-2999(98)00908-X | - |
uc.controloAutoridade | Sim | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-0889-2977 | - |
crisitem.author.orcid | 0000-0003-0789-8637 | - |
crisitem.author.orcid | 0000-0001-8329-2333 | - |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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