GALANIN CONTRACTS AND RELAXES GUINEA-PIG AND CANINE INTESTINAL SMOOTH-MUSCLE CELLS THROUGH DISTINCT RECEPTORS

Background/Aims: Galanin induces a contraction or a relaxation of digestive smooth muscle. Receptors mediating these effects have not been pharmacologically characterized. The aim of the study was to evaluate properties of two specific galanin antagonists M15 and M35 on galanin effects on muscle cells. Methods: Isolated muscle cells were obtained separately from circular and longitudinal layers of guinea pig and dog ileums. Contraction was expressed as percentage decrease in cell length from control. Results: Galanin induced a contraction of cells from guinea pig circular layer (50% effective concentration [EC(50)], 80 pmol/L) and dog longitudinal layer (EC(50), 100 pmol/L). The antagonists inhibited galanin-induced contraction. The most potent was M15 (50% inhibitory concentration [IC50], 80 pmol/L in guinea pig; 90 pmol/L in dog) which was >M35 (IC50, 4 nmol/L in guinea pig; 1 nmol/L in dog). In dog circular layer, galanin inhibited cholecystokinin-induced contraction by relaxing the cells (EC(50), 3 pmol/L). The antagonists inhibited this relaxation. The most potent was M35 (IC50, 60 pmol/L) which was >M15 (IC50, 900 pmol/L). Conclusions: Galanin antagonists M15 and M35 inhibit the contraction and the relaxation induced by galanin with different potency, suggesting the presence of distinct galanin receptors in gastrointestinal tract that each mediates a specific effect.