title: The contractile effects of several substituted short analogues of porcine galanin in isolated rat jejunal and colonic smooth muscle strips.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical University of Gdańsk, Do Studzienki 38, 80-227 Gdańsk, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Umer
authors.forename: H
authors.initials: H
authors.lastname: Ługowska
authors.forename: J
authors.initials: J
authors.lastname: Sein-Anand
authors.forename: P
authors.initials: P
authors.lastname: Rekowski
authors.forename: J
authors.initials: J
authors.lastname: Ruczyński
authors.forename: J
authors.initials: J
authors.lastname: Petrusewicz
authors.forename: R P
authors.initials: RP
authors.lastname: Korolkiewicz
mesh_terms: 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
chemical_list: D010446:Peptide Fragments; D019004:Galanin