Analysis of the Motor Effects Of 13-Norleucine Motilin on the Rabbit, Guinea Pig, Rat, and Human Alimentary Tract in Vitro

The Leu13‐motilin (KW‐5139)‐evoked release of acetylcholine from enteric neurones in the rabbit duodenum

“…The phasic contraction was not affected either by atropine or tetrodotoxin, thereby indicating that LMT acts directly through stimulation of smooth muscle. Others have also suggested that the contraction evoked by motilin is mediated through the motilin receptor present on smooth muscle cells and not through cholinergic transmission (Strunz et al, 1975;Adachi et al, 1981;Ludtke et al, 1989;Satoh et al, 1990). This notion was given support in a receptor binding study using '25I-labelled motilin (Bormans et al, 1986) and a mechanical study using rabbit colonic myocytes (Hasler et al, 1992).…”

“…Motilin, a 22 amino acid polypeptide discovered in the mucosa of the upper small intestine of the hog (Brown et al, 1971;, was found to localize in both enterochromaffin cells and non-enterochromaffin cells (Helmstaedter et al, 1979). In vivo and in vitro studies have indicated that motilin causes contraction of gastrointestinal muscle in several species (Strunz et al, 1975;Itoh et al, 1976;Adachi et al, 1981;Ludtke et al, 1989), and initiates periods of contractile activity that are similar to the interdigestive migrating motor complex in the dog (Itoh et al, 1976;Inatomi et al, 1989) and man (Janssens et al, 1983).…”

“…Therefore, motilin is considered to increase gastrointestinal motor activity by stimulating a cholinergic pathway. However, in rabbit and human gastrointestinal smooth muscle strips (stomach, pylorus and duodenum), motilin produces contractile responses which are resistant to blockade of cholinergic transmission (atropine), and of nerve excitation and propagation (tetrodotoxin, Strunz et al, 1975;Adachi et al, 1981;Ludtke et al, 1989;Satoh et al, 1990). Thus, motilin may act directly on smooth muscle cells of the rabbit duodenum and jejunum, and human stomach and pylorus.…”

An Action of Erythromycin in the Intestine That Is Not Mediated via Motilin Receptors

“…The pharmacology of the action of erythromycin in the ileum was directly compared with action at previously characterized motilin receptors in the rabbit duodenum. 13,14 Substantially greater concentrations of erythromycin (approximately 100-fold) were required to reveal effects on nerve-mediated contractions of the guinea-pig ileum compared with effects on the longitudinal muscle of rabbit duodenum. Human motilin (up to 100 mol/L) and canine motilin (up to 30 mol/L) were ineffective in reducing the contractions of the ileum.…”

“…The contractions that are observed in rabbit intestine are primarily or exclusively through receptors on the muscle, a conclusion based on their insensitivity to reduction by tetrodotoxin (TTX) or muscarinic antagonists. 13,14 The in vivo action of erythromycin and motilin to trigger migrating motor complexes, which are nerve-mediated events, suggests that erythromycin should act at neural motilin receptors. In fact, an action of erythromycin on neurons of the rabbit antrum has been recently discovered.…”