Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: Implications for the regulation of hypoxia-induced secretion at early life
Entity
UAM. Departamento de Farmacología; Instituto de Investigación del Hospital de La Princesa (IP)Publisher
Elsevier B. V.Date
2015-03-15Citation
10.1016/j.ejphar.2015.01.025.
European Journal of Pharmacology 751.1 (2015): 1-12
ISSN
0014-2999; 1879-0712 (on line)DOI
10.1016/j.ejphar.2015.01.025.Funded by
This work was supported by the following grants to AGG: (1) SAF 2010-21795 and (2) SAF 2013-44108, Ministerio de Economía y Competitividad, Spain; (3) CABICYC; UAM/Bioibérica, Spain; (4) We thank the continued support of Fundación Teófilo Hernando, Madrid, SpainProject
Gobierno de España. SAF 2010-21795; Gobierno de España. SAF 2010-21795Editor's Version
http://dx.doi.org/10.1016/j.ejphar.2015.01.025Subjects
Bovine chromaffin cells; Hypoxia; Calcium; NNC 55-0396; Rat embryo chromaffin cells; Voltage activated calcium channels; MedicinaRights
© 2015. Published by Elsevier B.V.Abstract
Adrenal chromaffin cells (CCs) express high-voltage activated calcium channels (VACCs) of
the L, N and PQ subtypes; additionally, T-type low-VACCs are also expressed during embryo
and neonatal life. Effects of the more frequently used T channel blockers NNC 55-0396 (NNC),
mibefradil, and Ni2+ on the whole-cell Ba2+ current (IBa), the K+-elicited [Ca2+]c transients and
catecholamine secretion, have been studied in adult bovine CCs (BCCs) and rat embryo CCs
(RECCs). NNC, mibefradil, and Ni2+ blocked BCC IBa with IC50 of 1.8, 4.9 and 70 μM, while
IC50 to block IBa in RECCs were 2.1, 4.4 and 41 μM. Pronounced blockade of K+-elicited [Ca2+]c
transients and secretion was also elicited by the three agents. However, the hypoxia-induced
secretion (HIS) of catecholamine in RECCs was blocked substantially (75%) with thresholds
concentrations of NCC (IC20 to block IBa); this was not the case for mibefradil and Ni2+ that
required higher concentrations to block the HIS response. Thus, out of the three compounds,
NNC seemed to be an adequate pharmacological tool to discern the contribution of T channels
to the HIS response, without a contamination with high-VACCs blockade
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Google Scholar:Fernández Morales, José Carlos
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Fernando Padín, J.
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Vestring, Stefan
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Musial, Diego C.
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De Diego, Antonio Miguel G
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García, Antonio G.
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