Mechanisms of Galanin-induced Contraction of Isolated Rat Gastric Fundus Strips†

Author： Korolkiewicz R.P. Konstañski Z. Rekowski P. Ruczyñski J. Szyk A. Szczepañska R. Korolkiewicz K.Z. Petrusewicz J.

Publisher： Pharmaceutical Press

ISSN： 1460-8081

Source： Pharmacy and Pharmacology Communications, Vol.6, Iss.9, 2000-09, pp. : 415-420

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Abstract

Galanin (Gal) constricts rat gastric fundus by acting on receptors located in the cell membrane. We compared the role of intracellular Ca²⁺ release with extracellular Ca²⁺ influx in Gal-stimulated contraction of isolated gastric smooth muscle strips. We also tested if phospholipase C (PLC) or protein kinase C (PKC) participate in the signal transduction cascade.Concentration–contraction curves were constructed non-cumulatively in the presence of atropine, hexamethonium, guanethidine and tetrodotoxin. The half-maximum effective concentration (EC50) of Gal was 21·62 nM and Hill’s coefficient was 1·02. The effects of Gal were decreased by diltiazem, Ca²⁺-deficiency in the buffer, Ca²⁺ removal from the extracellular medium or quercetin. Depletion of intracellular Ca²⁺-stores, ryanodine and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester diminished the contractile effect of Gal concentration-dependently. Trifluoroperazine and phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, neomycin and U-73122, attenuated the gastric fundus response to Gal, whereas phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD) blockers, D609 and propranolol, were ineffective. The inhibitors of PKC or myosin light chain kinase, calphostin C, chelerythrine, ML-7 and ML-9, lowered the myogenic activity of Gal.Our data confirmed that the stimulation of Gal receptors in gastric fundus is coupled to Ca²⁺ influx through voltage-dependent channels and intracellular Ca²⁺ release from ryanodine- and inositol 1,4,5-triphosphate-sensitive stores. Enzymes such as PI-PLC and PKC, but not PC-PLC or PLD, play a role in the signal transduction cascade. Calmodulin and myosin light chain kinase lie downstream of the increases in intracellular Ca²⁺ concentration evoked by Gal.