The contractile effects of several substituted short analogues of porcine galanin in isolated rat jejunal and colonic smooth muscle strips.
The activity of short porcine galanin (Gal) analogues was tested in vitro using rat jejunal and colonic smooth muscle strips. Peptides evoked concentration-dependent tissue contractions yielding typical response curves in concentration range from 0.3 nM to 300 microM, with a characteristic fall-down effect at the supramaximal concentrations. Gal(1-15) was less potent than Gal(1-29). Furthermore, [D-Trp(2)]Gal(1-15), [endo-Trp(2),Cle(4)]Gal(1-15), [D-Leu(4)]Gal(1-15), [des-Leu(4)]Gal(1-15), [Hse(6)]Gal(1-15), [Dab(14)]Gal(1-15), [Dpr(14)]Gal(1-15) or [Arg(14)]Gal(1-15) showed a considerable decrease in potency compared to Gal(1-15) in jejunal and/or colonic smooth muscle cells. Functional evidence confirmed that the integrity of both N- and C-terminals must be preserved in order to preserve a full excitatory myogenic potential of the peptide in rat jejunum and colon. Besides, amino acids located in positions 2, 4, 6 and 14 play a crucial role in recognition and activation of molecular domains responsible for Gal action in the intestinal smooth muscle.
Umer
A
A
Department of Pharmacology, Medical University of Gdańsk, Do Studzienki 38, 80-227 Gdańsk, Poland.
Ługowska
H
H
Sein-Anand
J
J
Rekowski
P
P
Ruczyński
J
J
Petrusewicz
J
J
Korolkiewicz
R P
RP
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019004:Galanin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013552:Swine
D010446:Peptide Fragments; D019004:Galanin