title: In vitro pharmacological actions of sinomenine on the smooth muscle and the endothelial cell activity in rat aorta.
abstract: Vasodilating actions of sinomenine were examined using rat aorta ring strips. Sinomenine (0.1 to 100 microM) dilated norepinephrine (NE, 5 microM)-induced vasoconstriction in a concentration-dependent manner reaching 68.8+/-5.1% (n=6, P<0.01) at a concentration of 100 microM. Sinomenine (100 microM) also attenuated KCl (60 mM) and phorbol 12, 13-dibutyrate (PDB, a protein kinase C, PK-C, activator, 300 nM)-induced vasoconstriction by 86.9+/-8.5% (n=6, P<0.01) and 49.9+/-9.8% (n=6, P<0.01), respectively. Pretreatment with nicardipine (a Ca2+ channel antagonist), staurosporine (a PK-C inhibitor), NG-monomethyl-L-arginine acetate (L-NMMA, a nitric oxide, NO, synthesis inhibitor), and indomethacin (a cyclooxygenase inhibitor) were carried out. Nicardipine (0.1 microM) led to a significant decrease in the vasodilating potential of sinomenine (at 100 microM, 68.8+/-5.1% vs. 35.5+/-6.9%; n=5, P<0.001). Pretreatment with staurosporine (30 nM) reduced sinomenine-associated vasodilation from 68.8+/-5.1% to 49.5+/-7.7% (n=5, P<0.001), and L-NMMA (100 microM) and indomethacin (10 microM), to 25.3+/-2.3% (n=5, P<0.001) and to 37.1+/-9.3% (n=5, P<0.001), respectively. The responses were almost similar to the results without endothelium. Therefore, these results indicate that sinomenine causes the vasorelaxation by the mechanisms involved with the inhibitions of Ca2+ channel and PK-C activity, and also with the activations of NO and prostaglandin (PG) I2 syntheses in endothelium.
authors.affiliation: Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, School of Medicine, Kashihara, Nara 634-8521, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Nishida
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Satoh
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents
chemical_list: D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009019:Morphinans; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C009271:sinomenine; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C