Lysine14galanin(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 galanin [pGal(1-29)-NH2] analogue [Lys14]pGal(1-15)-NH2 on rat gastric fundus. [Lys14]pGal(1-15)-NH2 is a less potent contractile agent than 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. Concentration-contraction curves were constructed for pGal(1-29)-NH2 alone (control) and pGal(1-29)-NH2 in the presence of 10, 100, and 1,000 nmol/l of [Lys14]pGal(1-15)-NH2. [Lys14]pGal(1-15)-NH2 shifted the concentration-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. [Lys14]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 pGal(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 pA2 value for [Lys14]pGal(1-15)-NH2 was 8.23. [Lys14]pGal(1-15)-NH2 seems to be a partial Gal receptor agonist. Since the lack of specific Gal receptor antagonists in the gastrointestinal tract makes a precise characterization of its role as a motility modulator difficult, the position 14 in the pGal(1-29)-NH2 molecule looks as an attractive target in the search of a pure Gal receptor antagonist in the smooth muscles of the gut.
Korolkiewicz
R
R
Department of Pharmacology, University of Gdańsk, Poland. kokor@amedec.amg.gda.pl
Sliwiński
W
W
Rekowski
P
P
Szyk
A
A
Mucha
P
P
Konstański
Z
Z
Korolkiewicz
K Z
KZ
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D019004:Galanin / Q000819:agonists / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists*
D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D019004:Galanin