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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.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2015 Mar 15; Vol. 751, pp. 1-12. Date of Electronic Publication: 2015 Jan 23. - Publication Year :
- 2015
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Abstract
- Adrenal chromaffin cells (CCs) express high-voltage activated calcium channels (high-VACCs) of the L, N and PQ subtypes; in addition, 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-VACC blockade.<br /> (Copyright © 2015. Published by Elsevier B.V.)
- Subjects :
- Animals
Animals, Newborn
Barium metabolism
Benzimidazoles pharmacology
Calcium Channels metabolism
Cattle
Cell Hypoxia drug effects
Chromaffin Cells cytology
Chromaffin Cells metabolism
Cyclopropanes pharmacology
Cytosol drug effects
Cytosol metabolism
Dose-Response Relationship, Drug
Membrane Potentials drug effects
Mibefradil pharmacology
Naphthalenes pharmacology
Nickel pharmacology
Potassium pharmacology
Rats
Calcium metabolism
Calcium Channel Blockers pharmacology
Catecholamines metabolism
Chromaffin Cells drug effects
Exocytosis drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 751
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 25622555
- Full Text :
- https://doi.org/10.1016/j.ejphar.2015.01.025