Prostaglandin synthesis elicited by adrenergic stimuli in rabbit aorta is mediated via alpha-1 and alpha-2 adrenergic receptors.
The purpose of this study was to characterize the type of adrenergic receptor(s) involved in both prostaglandin (PG) synthesis and the contractile response elicited by adrenergic receptor agonists in the rabbit aorta. The synthesis of prostacyclin as measured by the production of 6-keto-PGF1 alpha was assessed in vitro after exposing the aortic rings to different adrenergic agonists. Norepinephrine (NE), selective alpha 1 adrenergic receptor agonists methoxamine (MET), phenylephrine (PHE) and cirazoline (CIR) and the alpha 2 adrenergic receptor agonists UK 14304 (UK) and xylazine (XYL), but not the beta adrenergic receptor agonist isoproterenol (ISP), enhanced 6-keto-PGF1 alpha synthesis in a concentration-dependent manner with following order of potency: NE greater than UK 14304 greater than XYL greater than PHE greater than MET greater than CIR. The NE-induced increased in 6-keto-PGF1 alpha synthesis was attenuated by the alpha 1 adrenergic receptor antagonists prazosin (PZ) and corynanthine (COR) and by the alpha 2 adrenergic receptor antagonists rauwolscine (RW) and yohimbine (YOH). MET-induced 6-keto-PGF1 alpha synthesis was reduced by PZ and COR but not by RW. UK-induced 6-keto-PGF1 alpha synthesis was reduced by RW, YOH, and PZ, which also acts as alpha-2B receptor antagonist, but not by COR. In rabbit aortic rings, adrenergic agonists produced contraction with the following order of potency: NE greater than PHE greater than MET greater than CIR greater than UK greater than XYL.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis.
Malik
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D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D015121:6-Ketoprostaglandin F1 alpha