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

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

Author Fernandez-Morales, Jose C. Google Scholar
Fernando Padin, J. Google Scholar
Vestring, Stefan Google Scholar
Musial, Diego C. Autor UNIFESP Google Scholar
Diego, Antonio-Miguel G. de Google Scholar
Garcia, Antonio G. Google Scholar
Institution Univ Autonoma Madrid
Hosp Univ Princesa
Tech Univ Dresden
Universidade Federal de São Paulo (UNIFESP)
Abstract Adrenal chromaffin cells (CCs) express high voltage activated calcium channels (high-VACCs) of the L, N and PQ subtypes; in addition, T-Lype 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 vertical bar current (lBa), the K vertical bar -elicited ICa2 vertical bar]c transients and caLecholamine secretion have been studied in adult bovine CCs (BCCs) and rat embryo CCs (RECCs). NNC, rnibefradil, and Ni2 + blocked BCC lBa with 1050 of 1.8, 4.9 and 70 mu M, while IC50 to block lBa in RECCs were 2.1, 44 and 41 Pronounced blockade of K I -elicited ICa2 I]c transients and secretion was also elicited by the three agents. However, the hypoxia-induced secretion (HIS) of caLecholamine iii 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-VACC blockade. (C) 2015 Published by Elsevier B.V.
Keywords Bovine chromaffin cells
Hypoxia
Calcium
NNC 55-0396
Rat embryo chromaffin cells
Voltage activated calcium channels
Language English
Sponsor Ministerio de Economia y Competitividad, Spain
CABICYC
UAM/Bioiberica, Spain
Fundacion Teofilo Hernando, Madrid, Spain
Grant number Ministerio de Economia y Competitividad, Spain: SAF 2010-21795
Ministerio de Economia y Competitividad, Spain: SAF 2013-44108
Date 2015-03-15
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 751, p. 1-12, 2015.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1-12
Origin http://dx.doi.org/10.1016/j.ejphar.2015.01.025
Access rights Closed access
Type Article
Web of Science ID WOS:000350389300001
URI http://repositorio.unifesp.br/handle/11600/38887

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