OPIOID INHIBITION OF NICOTINE-INDUCED CA-45(2+)-UPTAKE INTO CULTURED BOVINE ADRENAL-MEDULLARY CELLS

The ability of a number of opioid agonists and antagonists to affect nicotine-induced Ca-45(2+)-uptake into cultured bovine adrenal medullary cells has been investigated. High (10-mu-M) concentrations of the opioid agonist bremazocine produced a significant inhibition of nicotine-induced Ca-45(2+)-uptake throughout the 15 min time course examined. The opioid subtype-selectivity of this inhibition was investigated; mu and delta selective agonists produced only minor effects whereas the kappa selective agonist U50-488H and the endogenous opioid peptides dynorphin(1-13) and metorphamide almost abolished nicotine-induced Ca-45(2+)-uptake. The U50-488H inhibition was significant at 10 nM concentrations with an IC50 of approximately 1-mu-M. U50-488H inhibition could not be reversed or reduced by the opioid antagonists naxolone, diprenophine or Mr2266. Furthermore, Mr2266 and its optical isomer Mr2267 also produced marked inhibition of Ca-45(2+)-uptake. The inhibition was specific to nicotine-induced Ca-45(2+)-uptake in that a similar level of uptake evoked by potassium depolarization was unaffected by high concentrations of U50-488H. These data indicate that opioid inhibition of nicotine-induced Ca-45(2+)-uptake does not involve classical, stereospecific opioid receptors and suggests the involvement of a pharmacologically distinct opioid recognition site. It is speculated that this may be associated with the nicotine receptor-ionophore complex.