Relation of diltiazem binding sites to opioid receptor subtypes in the guinea-pig brain

Interactions between diltiazem and opioids in guinea-pig brain membrane preparations were examined. Diltiazem did not inhibit bindings of 3H-dihydromorphine (3H-DHM), 3H-ethylketocyclazocine (3H-EKCZ) and 3H-naloxone (3H-NOX) but inhibited binding of 3H-[D-Ala2, D-Leu5]-enkephalin (3H-DADLE). In 3H-DADLE binding, diltiazem decreased the reciprocal indices of affinity (Kd values) of 3H-DADLE without changing on the maximal saturable binding (B. max) in guinea-pig brain membranes. These effects of diltiazem on the binding of 3H-DADLE were enhanced by 2.5mM CaCl2. Morphine, EKCZ, naloxone and even DADLE did not change the binding of 3H-diltiazem. These results suggest that the current of information concerning diltiazem and DADLE binding sites is one-way only so that no interaction exists.