anandamide and 4-desmethoxyverapamil

We examined the effects of anandamide (N-arachidonoylethanolamine) on the binding of three types of Ca2+ channel antagonists for L-type Ca2+ channel, i.e., 1,4-dihydropyridine, 1,5-benzothiazepine and phenylalkylamine, to rabbit skeletal muscle membranes. Anandamide inhibited the binding of all three ligands. Arachidonic acid, a putative metabolite or a precursor of anandamide, inhibited 1,4-dihydropyridine binding, whereas it augmented both 1,5-benzothiazepine and phenylalkylamine binding. The involvement of prostaglandins synthesized from arachidonic acid was considered to be minor. These findings indicate that both anandamide and arachidonic acid interact not only with 1,4-dihydropyridine but also with 1,5-benzothiazepine and phenylalkylamine binding sites as a common feature of unsaturated lipids.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Calcium Channel Blockers; Calcium Channels; Diltiazem; Endocannabinoids; Isradipine; Male; Polyunsaturated Alkamides; Rabbits; Verapamil