Direct contractile effect of motilin on isolated smooth muscle cells of guinea pig small intestine

Abstract

We examined the direct effect of motilin on longitudinal and circular smooth muscle cells isolated from the guinea pig small intestine. In addition, the effects of 8-( N, N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8, an inhibitor of intracellular Ca 2+-release), verapamil (a voltage-dependent Ca 2+-channel blocker), and removal of extracellular Ca 2+ were investigated to evaluate the role of intracellular Ca 2+ stores and extracellular Ca 2+ on the muscle contraction induced by motilin. The effects of atropine (a muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and loxiglumide (a CCK-receptor antagonist) were also examined to determine whether the motilin-induced contraction was independent of those receptors. Motilin induced a contraction of the longitudinal and circular smooth muscle cells in a dose-dependent manner with the maximal effect attained after 30 seconds of incubation. The ED 50 values were 0.3 nM and 0.05 nM, respectively. TMB-8 suppressed completely the motilin-induced contraction of both types of smooth muscle cells. Verapamil had only a slight suppressive effect. Removal of extracellular Ca 2+ did not have any significant influence on motilin-induced contraction. The contractile response to motilin was not affected by atropine, spantide or loxiglumide. Our findings showed that: 1) motilin has a direct contractile effect on both longitudinal and circular smooth muscle cells; 2) this contractile effect is not evoked via muscarinic, substance P or CCK receptors, and 3) the intracellular release of Ca 2+ plays an important role in the contractile response to motilin on both types of smooth muscle cells.