GALANIN, GALANTIDE AND GALANIN(1-14)-[ALPHA-AMINOBUTYRIC ACID(8)]-SCYLIORHININ-I - STRUCTURE-DEPENDENT EFFECTS ON THE RAT ISOLATED GASTRIC FUNDUS

The study was undertaken using selected pharmacodynamic parameters to describe the effects of porcine galanin(1-29)-NH2; porcine galanin fra gments; galantide; porcine galanin(1-14)-[alpha-aminobutyric acid(8)]s cyliorhinin-I and the analogues of the latter peptides on rat isolated gastric fundus muscle. All tested peptides, apart from galanin(16-29) -NH2 evoked reproducible concentration-dependent contractions with sig nificantly decreased activities in comparison to the potency of the na tive galanin(1-29)-NH2 molecule. The order of the contractile ability in the group of galanin(1-29)-NH2 short fragments was as follows: H2>g alanin(1-15)-OH>galanin(1-15)-NH2>[glycine(5)] -15)-NH2>[glycine(5),ly sine(14)]galanin(1-15)-NH2. Aside from [lysine(14)]galanin(1-15)-NH2 w hich had a lower efficacy, none of the peptides showed significant cha nges in this respect in comparison to the intact galanin(1-29)-NH2 mol ecule. The concentration-response curves of the tested peptides were t o the right and their slopes besides from: galanin(1-15)-OH; galanin(2 -15)-NH2; [glycine(5)]galanin(1-15)-NH2 remained not significantly dif ferent from galanin(1-29)-NH2. Hill's coefficient for galanin(1-29)-NH 2 is 1.03 indicating an interaction of one galanin(1-29)-NH2 molecule with one receptor, fulfilling criteria of classical receptor theory. F or galanin fragments Hill's coefficients are <1 implying that the rule s of classical theory may not apply. Galantide and analogues exhibited a subsequent decrease in potency: [cycloleucine(4)] (6)]galantide>[ph enylalnine(4fluor)(17)]galantide. Galanin(1-14)-[alpha-aminobutyric ac ids]-scyliorhinin-I and its analogues contracted the gastric fundus wi th a decline in strength: ]-scyliorhinin-I>galanin(1-14)-[alpha-aminob utyric ]-scyliorhinin-I>galanin(1-13)-[alpha-aminobutyric acid(8), nor leucine(10)]-scyliorhinin-I(3-10). They all displayed a greater effica cy than galanin(1-29)-NH2, and the concentration-response curves were slightly to the right, almost parallel to that of galanin(1-29)-NH2. S lopes of the curves were not significantly different from galanin(1-29 )-NH2. Hill's coefficient for the galantide, [cycloleucine(4)]galantid e; [homoserine(6)] galantide; [phenylalanine(4fluor)(17)]galantide and in(1-13)-[phenylalanine(4fluor)(7)]-scyliorhinin-I are <1. Hill's coe fficients for lanin(1-13)-[norleucine(10)]-scyliorhinin-I(3-10); galan in(1-14)[alpha-aminobutyric acid(8)]-scyliorhinin-I; galanin(1-14)-[al pha-aminobutyric acids, norleucine(10)]scyIiorhinin-I(3-10) are >1. A Hill's coefficient markedly different from 1 might indicate that an ac tivation of more than one type of receptors, negative or positive rece ptor cooperativity or multiple-step agonist-receptor reaction. (C) 199 7 The Italian Pharmacological Society.