Actions of galanin and some of its analogues on rat isolated gastric fundus

Summary— The study was undertaken to characterize the effects of porcine galanin (pGal) and some of its analogues on rat gastric fundus muscle strips. pGal, galantide (M15) and pGal(1–14)-[Abu8]SCY-I evoked reproducible concentration-dependent contractions in concentrations of 1–300, 3–1,000 and 100–3,000 nM, respectively, with EC50 values of 13, 70 and 187 nM. Hill's coefficient for pGal is 1.03, indicating an interaction of one pGal molecule with one receptor, fulfilling criteria of classical receptor theory. For M15 and pGal(1–14)-[Abu8]SCY-I, Hill's coefficients are significantly different from 1, namely 0.73 and 1.56, so that one drug molecule may not interact with one receptor. The stimulatory effects of pGal were not modified by dibenamine 10 μM or glybenclamide 1 or 10 μM. Diltiazem 0.1, 1 and 10 μM, papaverine 0.1, 10 μM or dibutyryl cAMP (dib cAMP) 100 and 300 μM, blocked the contraction to pGal in a concentration-dependent manner, indicating an important role for the influx of extracellular calcium ions and regulation by cAMP the pGal-evoked contraction. Diltiazem, dibutyryl cAMP and papaverine were not competitive antagonists of pGal in the stomach smooth muscle.