title: Comparative effects of endothelin and phorbol 12-13 dibutyrate in rat aorta.
abstract: The vasoconstrictive properties of endothelin (ET-1) and the protein kinase C activator, phorbol 12-13 dibutyrate (PDB) were comparatively investigated in isolated rat aorta. ET-1 (0.3-100 nM) and PDB (10 nM-3 microM) induced a slowly developing sustained contraction in endothelium denuded aorta. Maximal contractions induced by ET-1 and PDB were unaffected by diltiazem (10 microM). Substantial contraction to ET-1 (30 nM) and PDB (0.1 microM) remained in calcium-free medium. Contractions of ET-1 and PDB in calcium-free medium were unaffected by intracellular calcium depletion induced by phenylephrine. Following the response to ET-1 and PDB in a calcium-free medium, an additional sustained contraction was observed after calcium (2.5 mM) was added to the bath. The protein kinase C inhibitor, H7 (100 microM) was more potent in inhibiting contractions induced by phenylephrine and KCl than the ones elicited by ET-1 and PDB. The other protein kinase C inhibitors i.e. staurosporine (50 nM) and phloretin (100 microM) inhibited to a similar extent all the agonists tested. These results suggest that protein kinase C may play an important role in mediating the contraction to ET-1 in rat aorta.
authors.affiliation: Institut Henri Beaufour Research Labs, LES ULIS, France.
authors.forename: M
authors.initials: M
authors.lastname: Auguet
authors.forename: S
authors.initials: S
authors.lastname: Delaflotte
authors.forename: P E
authors.initials: PE
authors.lastname: Chabrier
authors.forename: P
authors.initials: P
authors.lastname: Braquet
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D016232:Endothelins; D007546:Isoquinolines; D010455:Peptides; D010879:Piperazines; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D004110:Diltiazem; D019311:Staurosporine; D010693:Phloretin; D002118:Calcium