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 contraction and has been proposed to regulate the onset of phase III of the migrating motor complex in dogs and humans. The effects of motilin and OHM-11526, a motilin antagonist in rabbit smooth muscle strips, were examined in isolated canine and human jejunal circular smooth muscle cells using whole cell patch-clamp techniques with Ba2+ as the charge carrier. Effects of both drugs on inward current through L-type Ca2+ channels (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 jejunal circular smooth muscle cells by 43 +/- 20 and 45 +/- 11%, respectively, and OHM-11526 increased I-CaL by 54 +/- 8 and 54 +/- 14%, respectively. The increase in inward current was blocked by nifedipine and by guanosine 5'-O-(2-thiodiphosphate) but not by pertussis toxin. Washout of both drugs resulted in a further increase in I-CaL These data suggest that both motilin and OHM-11526 activate an I-CaL in human and canine jejunal circular smooth muscle cells through a CT protein-coupled mechanism.