Galanin and its analogues: A structure-activity relationship studies in rat isolated gastric smooth muscles

Summary Galanin (GAL), a 29-amino-acid-residue neuropeptide, modulates gastric smooth muscles activity by interacting with specific receptors. However due to the lack of specific antagonists in the gastrointestinal (GI) tract the actual level of GAL involvement in GI motility remains largely unknown. In our studies we have performed structure-activity relationship studies of two porcine galanin fragments, two chimeric galanin analogues and several 15-amino-acid-residue galanin analogues modified in positions 2, 3, 4, 6, 8 or 14, investigating their contractile action on rat isolated gastric fundus strips, employed as in vitro assay of peptides activity. Thus we intended to characterize the molecular domains of GAL responsible for binding and activation of GAL receptors in rat gastric smooth muscle cells. The data acquired in the course of our structure-activity relationship studies suggest that both N-and C-terminal fragment of GAL molecule contribute towards the affinity and activity of GAL gastric smooth muscle cell receptors. Moreover, we concluded that positions 2, 3, 4, 6, 8 and 14 in the amino acid sequence of GAL may play important roles in binding and activation of GAL receptors in rat gastric smooth muscle cells. Abbreviations: The symbols of the amino acids, peptides and their derivatives are in accordance with the 1983 Recommendations of the IUPAC-IUB Joint Commission on Biochemical Nomenclature (Eur. J. Biochem. 138, 9 (1984)). Other symbols