Uses
U 46619 is a PGH2 analog that may be used as a thromboxane A2 (TP) receptor agonist affecting mitogenic growth of vascular smooth muscle in humans.
Biological Activity
PGH 2 (TXA 2 ) analog that is a potent and stable thromboxane A 2 (TP) receptor agonist (EC 50 = 0.035 μ M). Potently stimulates TP receptor-mediated, but not other prostaglandin receptor-mediated responses in various in vitro preparations. Activates ERK-1 and ERK-2 in HEK-293 cells expressing TP α and TP β receptors.
Biochem/physiol Actions
Thromboxane receptor agonist.
in vitro
u46619 showed a biphasic effect on human platelets. shape change and mlcp occurred at low concentrations of this compound (ec50 = 0.035 um and 0.057 um), whereas serotonin release, platelet at higher concentrations (ec50 = 0.536 um and 1.31 um). the effect on platelet shape change and mlcp is receptor mediated [3].
in vivo
u46619, through activation of eta and etb receptors, elicits renal cortical vasoconstriction and medullary vasodilation in the rat [2]. in conscious shr (spontaneously hypertensive rats), 1-100 nmol/kg u-46619 (i.c.v.) induced a dose-related increase in blood pressure but had no significant effect on heart rate [1].
References
[1] sirén al, svartstrm-fraser m, paakkari i. central cardiovascular effects of the endoperoxide analogue u-46619 in rats. prostaglandins leukot med. 1985 mar; 17 (3): 381-6.
[2] hantz h, adesuyi a, adebayo o. differential effects of u46619 on renal regional hemodynamics in the rat: involvement of endothelin. j pharmacol exp ther. 2001 oct; 299 (1): 372-6.
[3] morinelli ta1, niewiarowski s, daniel jl, smith jb. receptor-mediated effects of a pgh2 analogue (u 46619) on human platelets. am j physiol. 1987 nov; 253 (5 pt 2): h1035-43.
