Contractile action of galanin analogues on rat isolated gastric fundus strips is modified by tachyphylaxis to substance P.
This study was undertaken to characterize the interaction of porcine galanin (Gal) and some of its analogues with their receptors on rat gastric fundus muscle strips. Gal, galantide (M15) and Gal(1-14)-[Abu8]SCY-I evoked concentration-dependent contractions of gastric smooth muscle strips. Reproducible effects were observed in concentrations of 1-300, 3-1000 and 100-3000 nM, respectively. Specific EC50 for the contractile effect equalled 13.70 and 187 nM. Hill's coefficient for Gal is 1.03 indicating an interaction of one Gal molecule with one receptor, fulfilling the criteria of classical receptor theory. For M15 and Gal(1-14)-[Abu8]SCY-I Hill's coefficients are different from 1, namely 0.73 and 1.56, pointing out that the principle of interaction of one drug molecule with one receptor may not apply. The contraction induced by 300 nM of Gal was not significantly modified by tachyphylaxis to substance P (SP). On the contrary the introduction of tachyphylaxis to SP decreased the contractile effects of M15 and Gal(1-14)-[Abu8]SCY-I by about 57.7 +/- 3% and 39.6 +/- 5%, respectively. The findings suggest that contractile actions of M15 and Gal(1-14)-[Abu8]SCY-I are probably not only due to their agonist activities at Gal receptors but may result from a subsequent stimulation of receptors for SP or release of endogenous SP.
Korolkiewicz
R
R
Department of Pharmacology, Medical University of Gdańsk, Poland.
Sliwiński
W
W
Rekowski
P
P
Halama
A
A
Mucha
P
P
Szczurowicz
A
A
Guzowski
P
P
Korolkiewicz
K Z
KZ
D000595:Amino Acid Sequence; D000818:Animals; D019004:Galanin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology*; D013552:Swine; D013618:Tachyphylaxis / Q000502:physiology*
D013373:Substance P; D019004:Galanin