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Effect of Voltage‐Dependent Calcium Channel Blockers on Ethanol‐Induced β‐Endorphin Release From Hypothalamic Neurons in Primary Cultures
Author(s) -
De Alok,
Boyadjieva Nadka Iv.,
Sarkar Dipak K.
Publication year - 1999
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1999.tb04193.x
Subject(s) - nifedipine , flunarizine , channel blocker , voltage dependent calcium channel , calcium channel , chemistry , calcium channel blocker , pharmacology , dihydropyridine , calcium , endocrinology , medicine , neurotransmission , receptor , biochemistry
The voltage‐dependent calcium channel (VDCC) has been shown to mediate calcium entry into neurons that regulates neurotransmission in many neuronal cells. Four major types of VDCCs (three high‐voltage‐activated L‐. N‐. and P‐types and one low‐voltage‐activated T‐type) have been identified in neurons. Involvement of the VDCC in ethanol‐stimulated β‐endorphin (β‐EP) release from hypothalamic neurons has not been studied. In the present study, the role of VDCC on basal and ethanol‐induced β‐EP release was determined by using rat fetal hypothalamic cells in primary cultures. Treatments with a 50 mM dose of ethanol for 3 hr increased immunoreactive β‐EP (IR‐β‐EP) release from hypothalamic cells maintained in cultures for 9 days. Ethanol‐induced IR‐β‐EP release was inhibited by a P/Q‐type channel blocker ω‐agatoxin TK (0.1–1 μM). an N‐type channel blocker ω‐conotoxin (0.1‐1 μM), an L‐type blocker nifedipine (1‐10 μM), and a T‐type blocker flunarizine (1‐10 μpM). The minimal effective doses of these blockers that blocked the ethanol response produced no significant effects on basal release of IR‐β‐EP; neither did these doses of the blockers produce any significant effects on cell viability. These results suggest that ethanol‐stimulated IR‐β‐EP release is regulated by extracellular calcium involving β‐, N‐, L‐ and T‐type channels.