LYSINE(14)GALANIN(1-15)-NH2 - A PARTIAL AGONIST AT GALANIN RECEPTORS IN RAT ISOLATED GASTRIC FUNDUS

The study was undertaken to characterize the effects of the porcine ga lanin [pGal(1-29)-NH2] analogue [Lys(14)]pGal(1-15)-NH2 on rat gastric fundus. [Lys(14)]pGal(1-15)-NH2 is a less potent contractile agent th an pGal(1-29)-NH2 (EC50 74.1 vs. 43.7 nmol/l, respectively) and shows a significantly lower maximal response than pGal(1-29)-NH2. Concentrat ion-contraction curves were constructed for pGal(1-29)-NH2 alone (cont rol) and pCal(1-29)-NH2 in the presence of 10, 100, and 1,000 nmol/l o f [Lys(14)]pGal(1-15)-NH2. [Lys(14)]pGal(1-15)NH2 shifted the concentr ation-contraction curves of pGal(1-29)-NH2 significantly to the right, whereas their linear portions remained parallel to that for the pGal( 1-29)-NH2 control. [Lys(14)]pGal(1-15)-NH2 markedly increased the EC50 of the respective pGal(1-29)-NH2 concentration-contraction curves. It did not substantially change the maximal response of the muscles to p Gal(1-29)-NH2 and the form of the respective concentration-contraction curves. Schild's plot gave a straight line with a slope of 0.84. The pA(2) value for [Lys(14)]pGal(1-15)-NH2 was 8.23. [Lys(14)]pGal(1-15)- NH2 seems to be a partial Gal receptor agonist. Since the lack of spec ific Gal receptor antagonists in the gastrointestinal tract makes a pr ecise characterization ofits role as a motility modulator difficult, t he position 14 in the pGal(1-29)-NH2 molecule looks as an attractive t arget in the search of a pure Gal receptor antagonist in the smooth mu scles of the gut.