Prostaglandin synthesis elicited by adrenergic stimuli in rabbit aorta is mediated via alpha-1 and alpha-2 adrenergic receptors

C. Nebigil, Kafait Malik

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Abstract

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-PGF(1α) 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-PGF(1α) synthesis in a concentration-dependent manner with following order of potency: NE > UK 14304 > XYL > PHE > MET > CIR. The NE-induced increased in 6-keto-PGF(1α) 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-PGF(1α) synthesis was reduced by PZ and COR but not by RW. UK-induced 6-keto-PGF(1α) 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 > PHE > MET > CIR > UK > XYL. These data suggest that the contraction elicited by NE in the isolated rabbit aorta is mediated predominantly due to activation of alpha-1 adrenergic receptors, whereas 6-keto-PGF(1α) synthesis elicited by adrenergic agonists in rabbit aortic rings is mediated mainly by alpha-2, most likely alpha-2B subtypes of adrenergic receptors. Removal of endothelium did not alter NE-, and UK- or MET-induced 6-keto-PGF(1α) synthesis, suggesting that adrenergic receptors linked to PG synthesis in the rabbit aorta are located in the vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume254
Issue number2
StatePublished - 1990

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Adrenergic alpha-2 Receptors
Yohimbine
Prostaglandins F
Adrenergic Agents
Prostaglandins
Aorta
Methoxamine
Rabbits
Norepinephrine
Adrenergic Agonists
Xylazine
Prazosin
Phenylephrine
Adrenergic Receptors
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-1 Receptors
Adrenergic beta-Agonists

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Prostaglandin synthesis elicited by adrenergic stimuli in rabbit aorta is mediated via alpha-1 and alpha-2 adrenergic receptors",
abstract = "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-PGF(1α) 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-PGF(1α) synthesis in a concentration-dependent manner with following order of potency: NE > UK 14304 > XYL > PHE > MET > CIR. The NE-induced increased in 6-keto-PGF(1α) 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-PGF(1α) synthesis was reduced by PZ and COR but not by RW. UK-induced 6-keto-PGF(1α) 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 > PHE > MET > CIR > UK > XYL. These data suggest that the contraction elicited by NE in the isolated rabbit aorta is mediated predominantly due to activation of alpha-1 adrenergic receptors, whereas 6-keto-PGF(1α) synthesis elicited by adrenergic agonists in rabbit aortic rings is mediated mainly by alpha-2, most likely alpha-2B subtypes of adrenergic receptors. Removal of endothelium did not alter NE-, and UK- or MET-induced 6-keto-PGF(1α) synthesis, suggesting that adrenergic receptors linked to PG synthesis in the rabbit aorta are located in the vascular smooth muscle cells.",
author = "C. Nebigil and Kafait Malik",
year = "1990",
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journal = "Journal of Pharmacology and Experimental Therapeutics",
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T1 - Prostaglandin synthesis elicited by adrenergic stimuli in rabbit aorta is mediated via alpha-1 and alpha-2 adrenergic receptors

AU - Nebigil, C.

AU - Malik, Kafait

PY - 1990

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N2 - 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-PGF(1α) 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-PGF(1α) synthesis in a concentration-dependent manner with following order of potency: NE > UK 14304 > XYL > PHE > MET > CIR. The NE-induced increased in 6-keto-PGF(1α) 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-PGF(1α) synthesis was reduced by PZ and COR but not by RW. UK-induced 6-keto-PGF(1α) 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 > PHE > MET > CIR > UK > XYL. These data suggest that the contraction elicited by NE in the isolated rabbit aorta is mediated predominantly due to activation of alpha-1 adrenergic receptors, whereas 6-keto-PGF(1α) synthesis elicited by adrenergic agonists in rabbit aortic rings is mediated mainly by alpha-2, most likely alpha-2B subtypes of adrenergic receptors. Removal of endothelium did not alter NE-, and UK- or MET-induced 6-keto-PGF(1α) synthesis, suggesting that adrenergic receptors linked to PG synthesis in the rabbit aorta are located in the vascular smooth muscle cells.

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