Motilin receptors on isolated gastric smooth muscle cells

Abstract

Motilin has a stimulating effect on gastrointestinal motility. The mechanism of its action is not known. Direct and neuronal effects have been postulated. To determine if receptors are present on smooth muscle cells we investigated the effect of synthetic porcine motilin and its interaction with acetylcholine on isolated guinea pig gastric smooth muscle cells. Motilin elicited a dose-dependent contraction of gastric smooth muscle cells. Minimal (8.3 +/- 1.3%) and maximal (33.9 +/- 2.4%) responses were observed at 10(-12) and 10(-6) M, respectively. The ED50 of motilin was 10(-9) M. Acetylcholine also elicited a dose-response muscle contraction with a maximal response observed at 10(-7) M. Atropine (10(-7) M) completely inhibited the maximal response to acetylcholine but did not have any effect on the contractile response to motilin. In addition, dibutyryl guanosine 3',5'-cyclic monophosphate (10(-3) M) and substance P antagonist, spantide (10(-4) M), also did not inhibit the action of motilin. Acetylcholine (10(-11) M) shifted the dose-response curve of motilin to the left by 1.5 log units. The maximal response to the combination of motilin (10(-6) M) and acetylcholine (10(-11) M) was 32 +/- 3.2%, which was similar to the maximal response to motilin alone. It is concluded that distinct motilin and muscarinic receptors are present on guinea pig gastric smooth muscle cells. The interaction between motilin and acetylcholine is additive and not potentiative.