MOTILIN AND OHM-11526 ACTIVATE A CALCIUM CURRENT IN HUMAN AND CANINE JEJUNAL CIRCULAR SMOOTH-MUSCLE

Motilin is a potent agonist for gastrointestinal smooth muscle contrac tion and has been proposed to regulate the onset of phase III of the m igrating motor complex in dogs and humans. The effects of motilin and OHM-11526, a motilin antagonist in rabbit smooth muscle strips, were e xamined in isolated canine and human jejunal circular smooth muscle ce lls using whole cell patch-clamp techniques with Ba2+ as the charge ca rrier. Effects of both drugs on inward current through L-type Ca2+ cha nnels (I-CaL) in both canine and human cells were first observed at 10 (-8) M. At 10(-6) M, motilin increased I-CaL in canine and human jejun al circular smooth muscle cells by 43 +/- 20 and 45 +/- 11%, respectiv ely, and OHM-11526 increased I-CaL by 54 +/- 8 and 54 +/- 14%, respect ively. The increase in inward current was blocked by nifedipine and by guanosine 5'-O-(2-thiodiphosphate) but not by pertussis toxin. Washou t of both drugs resulted in a further increase in I-CaL These data sug gest that both motilin and OHM-11526 activate an I-CaL in human and ca nine jejunal circular smooth muscle cells through a CT protein-coupled mechanism.