INTERACTION OF OPIOID DRUGS WITH HUMAN PLATELET ALPHA(2)-ADRENOCEPTORS

Morphine, naltrexone and naloxone inhibited the binding of [H-3]clonidine to the alpha2-adrenoceptors in human platelet membranes, provided that Mg2+ was present in the medium. In the presence of 5'-guanylyl imidophosphate (Gpp(NH)p) or in the absence of Mg2+ morphine did not modify the binding of [H-3]clonidine. Neither [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAGO), nor [D-Pen2,D-Pen5]enkephalin (DPDPE), nor dynorphin-(1-17) affected the [H-3]clonidine binding. The presence of 1 mM naloxone did not alter the affinity of either [H-3]clonidine or [H-3]yohimbine, but reduced the number of binding sites of [H-3]clonidine, having no effect on [H-3]yohimbine. Naloxone inhibited the binding of adrenaline to high- but not low-affinity sites. It is concluded that morphine and semisynthetic antagonist derivatives interact with alpha2-adrenoceptors only in the high-affinity state.