STIMULATORY EFFECTS OF OPIOIDS ON TRANSMITTER RELEASE AND POSSIBLE CELLULAR MECHANISMS - OVERVIEW AND ORIGINAL RESULTS

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 in hibit adenylate cyclase, thus reducing neurotransmitter release. An in creasing body of evidence indicates an additional opposite, stimulator y activity of opioids. The present review summarizes the potentiating effects of opioids on transmitter release and the possible cellular ev ents underlying this potentiation: elevation of cytosolic calcium leve l (by either activating Ca2+ influx or mobilizing intracellular stores ), blockage of K+ channels and stimulation of adenylate cyclase. Bioch emical, 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 inv olvement of different subunits of these proteins, and the activation o f several intracellular signal transduction pathways. Among the many e xperimental preparations used to study the bimodal opioid activity, th e SK-N-SH neuroblastoma cell line is presented here as a suitable mode l for studying the complete chain of events leading from binding to re ceptors down to regulation of transmitter release, and for elucidating the molecular mechanism involved in the stimulatory effects of opioid agonists.