title: Pharmacological evaluation of GS-389, a novel tetrahydroisoquinoline analog related to higenamine, on vascular smooth muscle.
abstract: The effects of GS-389, a novel tetrahydroisoquinoline analog, on isolated rat and mouse thoracic aorta rings, were investigated. Both GS-389 and papaverine induced endothelium-independent, concentration-dependent relaxations of the rat and mouse aortae precontracted with phenylephrine (PE). The GS-389-induced inhibition of the contractile response to PE was noncompetitive. The initial phasic contraction to PE elicited in Ca(2+)-free media was also attenuated by pretreatment with GS-389, indicating that GS-389 may interfere with the release of intracellular Ca2+ and/or the effects of intracellular Ca2+ release. GS-389 potentiated the vasodilatory effects of isoproterenol and sodium nitroprusside in rat and mouse aortae. GS-389 significantly increased cGMP levels in the rat aorta and inhibited cGMP phosphodiesterase from the rabbit brain. Methylene blue, but not propranolol, inhibited the vasodilatory effect of GS-389. These results suggest that the vasorelaxant effect of GS-389 may be due, at least in part, to inhibition of cGMP metabolism.
authors.affiliation: Department of Pharmacology, College of Medicine, Gyeongsang National University, Chinju, Korea.
authors.forename: K C
authors.initials: KC
authors.lastname: Chang
authors.forename: J K
authors.initials: JK
authors.lastname: Lim
authors.forename: C W
authors.initials: CW
authors.lastname: Park
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001639:Bicarbonates / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D001639:Bicarbonates; D002316:Cardiotonic Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; C075361:GS 389; D004533:Egtazic Acid; D010208:Papaverine; D008751:Methylene Blue; C012348:higenamine