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5-Hydroxytryptamine (5-HT) and SK&F 103829 contract canine lower esophageal sphincter smooth muscle by stimulating 5-HT2 receptors. 1992

M S Barnette, and M Grous, and C D Manning, and W J Price, and A H Nelson, and W E Bondinell, and F C Barone, and H S Ormsbee
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.

Addition of 5-HT or SK&F 103829 (2,3,4,5 tetrahydro-8[methyl-sulfonyl]-1 H-3-benzazepin-7-ol hydrobromide) contracts isolated strips of canine lower esophageal sphincter (LES) circular smooth muscle. 5-HT acts directly on the smooth muscle, since pretreatment with the neurotoxin TTX does not inhibit this contraction. Depletion of extracellular calcium or pretreatment with nifedipine inhibited the contraction to both 5-HT and SK&F 103829. Therefore, in this smooth muscle, the contraction produced by both 5-HT and SK&F 103829 requires extracellular calcium and is sensitive to inhibition by a voltage-dependent Ca2+ channel antagonist. In addition, with respect to 5-HT, SK&F 103829 appeared to act as a partial agonist. Receptor alkylation studies using phenoxybenzamine demonstrated no receptor reserve for the contractile response to 5-HT. Nonsurmountable antagonism of the contraction induced by 5-HT and SK&F 103289 was observed with several 5-HT2 antagonists, i.e., methysergide, ketanserin, cyproheptadine, and LY 53857. Using a method established for pseudoirreversible antagonism, the Ki values for these 5-HT2 receptor antagonists were estimated. Results suggested that both 5-HT and SK&F 103829 contract the canine LES by interacting at the same receptor site and that this receptor site has characteristics of the 5-HT2 receptor. Finally, neither bulbocapnine, domperidone, nor prazosin significantly alters the response to 5-HT or SK&F 103829. Thus, isolated strips of canine LES contain a contractile 5-HT2 receptor, and SK&F 103829 behaves as a partial agonist at this site.

UI MeSH Term Description Entries
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004943 Esophagogastric Junction The area covering the terminal portion of ESOPHAGUS and the beginning of STOMACH at the cardiac orifice. Gastroesophageal Junction,Gastroesophageal Junctions,Junction, Esophagogastric,Junction, Gastroesophageal,Junctions, Gastroesophageal
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001552 Benzazepines Compounds with BENZENE fused to AZEPINES.

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