Stimulatory effects of opioids on transmitter release and possible cellular mechanisms: Overview and original results |
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Authors: | Yosef Sarne Anat Fields Ora Keren Mikhal Gafni |
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Institution: | (1) The Mauerberger Chair in Neuropharmacology, Sackler School of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel;(2) Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel |
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Abstract: | Opiates and opioid peptides carry out their regulatory effects mainly by inhibiting neuronal activity. At the cellular level,
opioids block voltage-dependent calcium channels, activate potassium channels and inhibit adenylate cyclase, thus reducing
neurotransmitter release. An increasing body of evidence indicates an additional opposite, stimulatory activity of opioids.
The present review summarizes the potentiating effects of opioids on transmitter release and the possible cellular events
underlying this potentiation: elevation of cytosolic calcium level (by either activating Ca2+ influx or mobilizing intracellular stores), blockage of K+ channels and stimulation of adenylate cyclase. Biochemical, pharmacological and molecular biology studies suggest several
molecular mechanisms of the bimodal activity of opioids, including the coupling of opioid receptors to various GTP-binding
proteins, the involvement of different subunits of these proteins, and the activation of several intracellular signal transduction
pathways. Among the many experimental preparations used to study the bimodal opioid activity, the SK-N-SH neuroblastoma cell
line is presented here as a suitable model for studying the complete chain of events leading from binding to receptors down
to regulation of transmitter release, and for elucidating the molecular mechanism involved in the stimulatory effects of opioid
agonists.
Special issue dedicated to Dr. Eric J. Simon. |
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Keywords: | Opioids transmitter release calcium cAMP potassium channels |
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