Title: GALANIN, GALANTIDE AND GALANIN(1-14)-[α-AMINOBUTYRIC ACID8]-SCYLIORHININ-I: STRUCTURE DEPENDENT EFFECTS ON THE RAT ISOLATED GASTRIC FUNDUS
Abstract: The study was undertaken using selected pharmacodynamic parameters to describe the effects of porcine galanin(1-29)-NH2; porcine galanin fragments; galantide; porcine galanin(1-14)-[α-aminobutyric acid8]scyliorhinin-I and the analogues of the latter peptides on rat isolated gastric fundus muscle. All tested peptides, apart from galanin(16–29)-NH2evoked reproducible concentration-dependent contractions with significantly decreased activities in comparison to the potency of the native galanin(1–29)-NH2molecule. The order of the contractile ability in the group of galanin(1-29)-NH2short fragments was as follows: [lysine14]galanin(1–15)-NH2>galanin(1–15)-OH>galanin(1–15)-NH2>[glycine5] galanin(1–15)-NH2>galanin(2–15)-NH2>[glycine5,lysine14]galanin(1–15)-NH2. Aside from [lysine14]galanin(1–15)-NH2which had a lower efficacy, none of the peptides showed significant changes in this respect in comparison to the intact galanin(1–29)-NH2molecule. The concentration-response curves of the tested peptides were to the right and their slopes besides from: galanin(1–15)-OH; galanin(2–15)-NH2; [glycine5]galanin(1–15)-NH2remained not significantly different from galanin(1–29)-NH2. Hill's coefficient for galanin(1–29)-NH2is 1.03 indicating an interaction of one galanin(1–29)-NH2molecule with one receptor, fulfilling criteria of classical receptor theory. For galanin fragments Hill's coefficients are <1 implying that the rules of classical theory may not apply. Galantide and analogues exhibited a subsequent decrease in potency: [cycloleucine4] galantide>galantide>[homoserine6]galantide>[phenylalnine(4fluor)17]galantide. Galanin(1–14)-[α-aminobutyric acid8]-scyliorhinin-I and its analogues contracted the gastric fundus with a decline in strength: galanin(1–13)-[norleucine10]-scyliorhinin-I(3–10)>galanin(1–13)-[phenylalanine(4fluor)7]-scyliorhinin-I>galanin(1–14)-[α-aminobutyric acid8]-scyliorhinin-I>galanin(1–13)-[α-aminobutyric acid8, norleucine10]-scyliorhinin-I(3–10). They all displayed a greater efficacy than galanin(1–29)-NH2, and the concentration-response curves were slightly to the right, almost parallel to that of galanin(1–29)-NH2. Slopes of the curves were not significantly different from galanin(1–29)-NH2. Hill's coefficient for the galantide, [cycloleucine4]galantide; [homoserine6]galantide; [phenylalanine(4fluor)17]galantide and galanin(1–13)-[phenylalanine(4fluor)7]-scyliorhinin-I are <1. Hill's coefficients for galanin(1–13)-[norleucine10]-scyliorhinin-I(3–10); galanin(1–14)-[α-aminobutyric acid8]-scyliorhinin-I; galanin(1–14)-[α-aminobutyric acid8, norleucine10]-scyliorhinin-I(3–10) are >1. A Hill's coefficient markedly different from 1 might indicate that an activation of more than one type of receptors, negative or positive receptor cooperativity or multiple-step agonist-receptor reaction.
Publication Year: 1997
Publication Date: 1997-01-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 13
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