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09 January 2002

Mechanism of the contractile effects of galantide and Galanin(1-14) [alpha-aminobutyric acid]scyliorhinin-I in rat isolated fundus strips.

Jaroslaw Dabrowski, Marek Ujda, Konstanty Zbigniew Korolkiewicz, Jaroslaw Ruczyński, Agnieszka Szyk, Piotr Rekowski, Zdziaław Konstanski, Roman P Korolkiewicz, Jacek Petrusewicz

Med Sci Monit 2002; 8(1): BR19-23 :: ID: 420976

Abstract

BACKGROUND: The study was undertaken to establish the pharmacological basis of the stimulatory activity of galantide (M15) and galanin(1-14)-(a-aminobutyric acid8-[Abu8])scyliorhinin-I [Scy-I] in gastric smooth muscle. MATERIAL/METHODS: Isotonic contractions of the isolated, longitudinal rat gastric fundus strips were recorded. RESULTS: Galanin, galanin(1-15)-NH2, M15 and galanin(1-14)-[Abu8]Scy-I elicited concentration-dependent contractions. Their EC50s equaled 12.95, 174, 70.06 and 187 nM respectively. Hill's coefficients for galanin and galanin(1-15)-NH2 were not different from unity, indicating an interaction of one peptide molecule with one receptor according to the principles of classical receptor theory. Hill's coefficients were 0.73 and 1.56 for M15 and galanin (1-14)-[Abu8]Scy-I, respectively, a value significantly different from unity. Cold-storage denervation, tetrodotoxin-TTX (1 mM), spantide (100 mM) and NK1-3 receptor antagonists SR140333, 48968, 142801 (up to 10 mM) notably diminished M15, galanin(1-14)-[Abu8]Scy-I, SP(5-11) and [Abu8]-Scy-I evoked contractions without affecting activities of galanin and galanin(1-15)-NH2. Additionally, cross-desensitization experiments attenuated activity of M15 and galanin(1-14)-[Abu8]Scy-I without any noticeable action on galanin or galanin(1-15)-NH2. CONCLUSIONS: The action of chimeric peptides on the smooth muscle of the rat gastrointestinal tract depended not only on the myogenic interaction of those peptides with galanin binding sites, but also on the activation of tachykinin receptors or the release of endogenous mediators from the presynaptic terminals.

Keywords: Binding Sites, Cold, Dose-Response Relationship, Drug, galanin, Muscle Contraction, Muscle, Smooth, Peptides, Rats, Wistar, Receptors, Tachykinin, Research Support, Non-U.S. Gov, Stomach, substance P

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750