Direct contractile effect of motilin on isolated smooth muscle cells from human gallbladder

To test the hypothesis that motilin receptors are present on smooth muscle cells of the human gallbladder, smooth muscle cells were isolated from the gallbladder and their direct contractile responses to motilin were examined. Motilin elicited a dose-dependent contraction of human gallbladder smooth muscle cells. Maximal contraction rate as defined by the percentage decrease in cell length was 23.7 +/- 0.7% at 10(-7) M for motilin and was similar to that for cholecystokinin octapeptide (CCK-OP) (24.2 +/- 1.5%) observed at 10(-10) M. The contractile sensitivity of gallbladder muscle cells to motilin (ED50 = 6 pM) was two orders of magnitude less than that to CCK-OP (ED50 = 0.07 pM). The motilin-induced contraction was inhibited in a dose-dependent manner by addition of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, an inhibitor of intracellular Ca2+ release. These results indicate that distinct motilin receptors are likely to be present on human gallbladder smooth muscle cells, as evidenced by their direct contractile responses, and suggest that Ca2+ release from intracellular calcium stores is important in the contractile response to motilin.