title: Genistein potentiates protein kinase A activity in porcine coronary artery.
abstract: Soy consumption is associated with a lower risk of atherosclerotic disease in the oriental population. Genistein is a soy isoflavone bearing estrogenic properties. Previous experiments in our laboratory demonstrated the potentiation of endothelium-independent relaxation of coronary artery by both estrogen and genistein. The potentiating effects of both estrogen and genistein were mediated through the cAMP-signaling pathway. We hypothesize that genistein could enhance protein kinase A (PKA) activity in porcine coronary artery smooth muscle, thereby offering a mechanism for the potentiation of vascular relaxation by genistein. In our study, a high concentration of genistein (10(-4.5) M) significantly increased PKA activity in porcine coronary artery rings. While genistein at 10(-5.5) M and forskolin at 10(-7) M had no effect on PKA activity, the combination of the two compounds at the prescribed concentrations caused a significant increase in PKA activity. The increase in PKA activity by genistein was abolished by SQ 22536 (adenylate cyclase blocker), but not by NF 449 (Gs protein blocker) or ICI 182780 (estrogen receptor antagonist). Our results suggest that the action of genistein is mediated via adenylate cyclase, but does not appear to involve Gs protein or ICI 182780-sensitive estrogen receptor.
authors.affiliation: Department of Pharmacology, University of Hong Kong, 2/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong SAR, China.
authors.forename: William W H
authors.initials: WW
authors.lastname: Ng
authors.forename: Wendy
authors.initials: W
authors.lastname: Keung
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Xu
authors.forename: Kwok F J
authors.initials: KF
authors.lastname: Ng
authors.forename: George P H
authors.initials: GP
authors.lastname: Leung
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Choy
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001557:Benzenesulfonates / Q000378:metabolism / Q000494:pharmacology; D005576:Colforsin / Q000378:metabolism; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D019833:Genistein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013552:Swine
chemical_list: C110258:4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate); D001557:Benzenesulfonates; D004965:Estrogen Antagonists; D047428:Protein Kinase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D000077267:Fulvestrant; D004958:Estradiol; D019833:Genistein; D000225:Adenine