title: GM-109: a novel, selective motilin receptor antagonist in the smooth muscle of the rabbit small intestine.
abstract: The pharmacological properties of the cyclic peptide Phe-cyclo[Lys-Tyr(3-tBu)-beta Ala-].trifluoroacetate (GM-109), a selective motilin antagonist, were investigated in the smooth muscle of the rabbit small intestine. GM-109 (0.1-3 microM) competitively inhibited contractions induced by porcine motilin (pMTL) in rabbit isolated duodenum longitudinal strips, with a pA2 value of 7.37 +/- 0.24. However, the contractile response to acetylcholine, to substance P, to prostaglandin F2 alpha and to KCl was unaffected by 10 microM GM-109 in the same preparation. Both GM-109 and pMTL competitively inhibited 125I-pMTL binding to motilin receptors in a homogenate of the rabbit small intestinal smooth muscle tissue. The pKi value of GM-109 and the pKd value of unlabeled pMTL were 7.99 +/- 0.04 and 9.25 +/- 0.06 (each n = 5), respectively. These results indicate that GM-109 is a selective and competitive motilin receptor antagonist in the smooth muscle of the rabbit small intestine. Thus this compound may be a useful pharmacological tool for examining the functional role(s) of motilin.
authors.affiliation: Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takanashi
authors.forename: K
authors.initials: K
authors.lastname: Yogo
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: M
authors.initials: M
authors.lastname: Ikuta
authors.forename: M
authors.initials: M
authors.lastname: Akima
authors.forename: H
authors.initials: H
authors.lastname: Koga
authors.forename: H
authors.initials: H
authors.lastname: Nabata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D009037:Motilin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011869:Radioligand Assay; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C093574:GM 109; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin