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Stimulatory effects of opioids on transmitter release and possible cellular mechanisms: Overview and original results

  • Simulatory EfFects of Opioids
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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.

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Authors and Affiliations

  1. The Mauerberger Chair in Neuropharmacology, Sackler School of Medicine, Tel-Aviv University, 69978, Tel-Aviv, Israel

    Yosef Sarne, Anat Fields, Ora Keren & Mikhal Gafni

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  1. Yosef Sarne
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  2. Anat Fields
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  3. Ora Keren
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  4. Mikhal Gafni
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Special issue dedicated to Dr. Eric J. Simon.

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Sarne, Y., Fields, A., Keren, O. et al. Stimulatory effects of opioids on transmitter release and possible cellular mechanisms: Overview and original results. Neurochem Res 21, 1353–1361 (1996). https://doi.org/10.1007/BF02532376

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