title: Identification of a novel vasoconstrictor peptide specific for the systemic circulation.
abstract: Some small molecular weight peptides possess potent vasoactive properties. Herein we have identified the laminin nonapeptide (LNP) CDPGYIGSR as a novel vasoconstrictive agent. Isometric force measurements revealed that LNP induced vasoconstriction in small and large murine arteries in a dose-dependent fashion; LNP also increased vascular tone in human mammary arteries. The vasoactive response was specific for the nonapeptide, because neither scrambled nor very similar peptide sequences modulated vascular tone. As an underlying mechanism we found in [Ca(2+)](i) imaging experiments that the nonapeptide induced transmembrane [Ca(2+)](i) influx in vascular smooth muscle cells. Patch clamp experiments showed that LNP activated nonselective cation channels, causing depolarization of the membrane potential and opening of L-type Ca(2+) channels. The functional effect of LNP was also assessed with catheter measurements in mice in vivo and confirmed vasoconstriction. This effect was restricted to the systemic circulation, because measurements with the perfused lung system demonstrated that LNP did not alter vascular tone in pulmonary arteries. Thus, LNP is a vasoconstrictor in mouse and human arteries, and its vasoactivity is restricted to the systemic vasculature.
authors.affiliation: Institute of Physiology I, University of Bonn, Bonn, Germany. bernd.fleischmann@uni-bonn.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Michaela
authors.initials: M
authors.lastname: Matthey
authors.forename: Jan C
authors.initials: JC
authors.lastname: Heinemann
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001775:Blood Circulation / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C470965:CDPGYIGSR; D015220:Calcium Channels; D007797:Laminin; D009842:Oligopeptides; D014662:Vasoconstrictor Agents; D002118:Calcium