Does motilin stimulate the gastrointestinal motility of the pig? In vitro study using smooth muscle strips and dispersed muscle cells.

To clarify the physiological role of motilin in the pig gastrointestinal (GI) tract, effect of Leu13-porcine motilin (LMT) on the contractility of GI smooth muscle was investigated in studies using isolated muscle strips and dispersed muscle cells. LMT produced no contraction in either longitudinal muscle (LM) or circular muscle (CM) of the stomach (fundus, corpus, antrum), duodenum, ileum and colon even at 1 microM. Pretreatment with LMT (1 nM-1 microM) did not potentiate the contractile response to acetylcholine (ACh) in each muscle strip. Dispersed cells from the duodenum responded to ACh in a concentration-dependent manner (EC50 = 10 pM), but not to LMT even at a high concentration (10 microM). Electrical field stimulation (EFS) caused a frequency-dependent (0.2-10 Hz) contraction of the duodenal LM that was almost completely inhibited by atropine or tetrodotoxin. EFS caused the relaxation of duodenal CM in a frequency-dependent manner (0.1-10 Hz). This relaxation was not inhibited by atropine, propranolol, phentolamine or guanethidine, indicating the involvement of noncholinergic, nonadrenergic (NCNA) nerves. NG-nitro L-arginine methylester (L-NAME, 100 microM) attenuated the EFS-induced relaxation and the inhibition at low frequency was larger than that at high frequency. L-Arginine prevented the inhibition by L-NAME but D-arginine did not. LMT (1 nM-1 microM) had no influence on EFS-induced cholinergic contraction of LM and EFS-induced NCNA relaxation of CM layer. The present in vitro studies indicate that motilin is ineffective in producing contraction and in modulating the autonomic neuroeffector transmission of the pig GI smooth muscle, and suggest that pig GI smooth muscle lacks functional motilin receptors.