title: Endothelium-dependent relaxation of rat aorta by butein, a novel cyclic AMP-specific phosphodiesterase inhibitor.
abstract: Butein, isolated from Dalbergia odorifera T. Chen, caused endothelium-dependent relaxation of rat aorta precontracted with phenylephrine. This effect was abolished in endothelium-denuded aorta and in endothelium-intact aorta in the presence of NG-monomethyl-L-arginine, oxyhemoglobin and methylene blue, whereas the effect was unaltered by indomethacin or charybdotoxin. These results indicate that the vasorelaxant effect of butein depended on the endothelium and was mediated by endothelium-derived relaxing factor (EDRF). Incubation of endothelium-intact aorta with butein increased not only cAMP but also cGMP content. Four phosphodiesterase forms were isolated by diethylaminoethyl (DEAE)-Sephacel chromatography from rat aorta. cAMP-specific phosphodiesterase (type IV) activity was potently inhibited by butein with an IC50 of 10.4 +/- 0.4 microM. In contrast, phosphodiesterase I, III and V activities were inhibited by butein above 100 microM. Adenylate cyclase and guanylate cyclase activities were unchanged by butein. These results suggest that the increase of cAMP formation elicited by butein is due to the inhibition of cAMP-specific phosphodiesterase. The specific phosphodiesterase IV inhibitor (rolipram) and V inhibitor (zaprinast) both produced endothelium-dependent relaxations, whereas the phosphodiesterase III inhibitor (trequinsin) produced relaxation of rat aorta independent of the endothelium. In the presence of a functional endothelium, relaxations produced by butein were significantly potentiated by isoprenaline, forskolin, trequinsin and sodium nitroprusside. It is concluded that butein, a novel cAMP-specific phosphodiesterase inhibitor, produced relaxation of rat aorta, an effect dependent on an intact endothelium. The relaxant effect of butein was markedly enhanced by cGMP-elevating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047188:Chalcones; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D010656:Phenylephrine; C040918:butein; D002599:Chalcone; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP