Prostaglandin synthesis elicited by adrenergic stimuli is mediated via alpha-2C and alpha-1A adrenergic receptors in cultured smooth muscle cells of rabbit aorta

C. Nebigil, Kafait Malik

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Abstract

This study was performed to characterize the subtype of adrenergic receptor(s) (AR) involved in prostacyclin synthesis [measured as 6-keto- prostaglandin (PG)F(1α)] elicited by AR agonists in cultured vascular smooth muscle cells of rabbit aorta. Both alpha-1 and alpha-2 AR agonists enhanced 6-keto-PGF(1α) synthesis in a dose-dependent manner with the following order of potency: norepinephrine > BHT 933 > UK 14304 > xylazine > phenylephrine ≥ methoxamine > cirazoline. Isoproterenol and oxymetazoline did not alter 6- keto-PGF(1α) synthesis. Methoxamine-induced 6-keto-PGF(1α) synthesis was not reduced by the alpha-2 AR antagonist rauwolscine. The affinities of AR antagonists (PA2 value) in inhibiting methoxamine-induced 6-keto-PGF(1α) synthesis were of the following order: prazosin > WB 4101 > corynanthine > yohimbine. Administration of WB 4101 and the irreversible alpha-1B AR antagonist chloroethylclonidine reduced norepinephrine (in the presence of rauwolscine, 10-8 M)- or methoxamine-induced 6-keto-PGF(1α) synthesis; WB 4101 was more potent than chloroethylclonidine. UK 14304-induced 6-keto- PGF(1α) synthesis was not reduced by chloroethylclonidine or BRL 44408, a selective alpha-2A AR antagonist, but it was inhibited by other alpha AR antagonists. The affinities of AR antagonists (PA2 values) in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis were of the following order: rauwolscine > yohimbine > BAM 1303 > BRL 41992 > WB 4101 > ARC 239 ≥ prazosin > SKF 104078 ≥ corynanthine. The order of affinity of alpha-2 AR antagonists in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis in vascular smooth muscle cells was similar to that derived from radioligand binding studies in opossum kidney cell line receptors classified as alpha-2C receptors. These data suggest that 6-keto-PGF(1α) synthesis elicited by adrenergic stimuli in cultured vascular smooth muscle cells of rabbit aorta is mediated primarily via alpha-2C and to a lesser extent alpha-1A receptors.

Original languageEnglish (US)
Pages (from-to)849-858
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume260
Issue number2
StatePublished - 1992

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Adrenergic alpha-1 Receptors
Prostaglandins F
Adrenergic Agents
Prostaglandins
Smooth Muscle Myocytes
Aorta
Yohimbine
Rabbits
Methoxamine
Vascular Smooth Muscle
Prazosin
Norepinephrine
Oxymetazoline
Xylazine
Opossums
Phenylephrine
Epoprostenol
Isoproterenol
Adrenergic Receptors

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Prostaglandin synthesis elicited by adrenergic stimuli is mediated via alpha-2C and alpha-1A adrenergic receptors in cultured smooth muscle cells of rabbit aorta",
abstract = "This study was performed to characterize the subtype of adrenergic receptor(s) (AR) involved in prostacyclin synthesis [measured as 6-keto- prostaglandin (PG)F(1α)] elicited by AR agonists in cultured vascular smooth muscle cells of rabbit aorta. Both alpha-1 and alpha-2 AR agonists enhanced 6-keto-PGF(1α) synthesis in a dose-dependent manner with the following order of potency: norepinephrine > BHT 933 > UK 14304 > xylazine > phenylephrine ≥ methoxamine > cirazoline. Isoproterenol and oxymetazoline did not alter 6- keto-PGF(1α) synthesis. Methoxamine-induced 6-keto-PGF(1α) synthesis was not reduced by the alpha-2 AR antagonist rauwolscine. The affinities of AR antagonists (PA2 value) in inhibiting methoxamine-induced 6-keto-PGF(1α) synthesis were of the following order: prazosin > WB 4101 > corynanthine > yohimbine. Administration of WB 4101 and the irreversible alpha-1B AR antagonist chloroethylclonidine reduced norepinephrine (in the presence of rauwolscine, 10-8 M)- or methoxamine-induced 6-keto-PGF(1α) synthesis; WB 4101 was more potent than chloroethylclonidine. UK 14304-induced 6-keto- PGF(1α) synthesis was not reduced by chloroethylclonidine or BRL 44408, a selective alpha-2A AR antagonist, but it was inhibited by other alpha AR antagonists. The affinities of AR antagonists (PA2 values) in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis were of the following order: rauwolscine > yohimbine > BAM 1303 > BRL 41992 > WB 4101 > ARC 239 ≥ prazosin > SKF 104078 ≥ corynanthine. The order of affinity of alpha-2 AR antagonists in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis in vascular smooth muscle cells was similar to that derived from radioligand binding studies in opossum kidney cell line receptors classified as alpha-2C receptors. These data suggest that 6-keto-PGF(1α) synthesis elicited by adrenergic stimuli in cultured vascular smooth muscle cells of rabbit aorta is mediated primarily via alpha-2C and to a lesser extent alpha-1A receptors.",
author = "C. Nebigil and Kafait Malik",
year = "1992",
language = "English (US)",
volume = "260",
pages = "849--858",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

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TY - JOUR

T1 - Prostaglandin synthesis elicited by adrenergic stimuli is mediated via alpha-2C and alpha-1A adrenergic receptors in cultured smooth muscle cells of rabbit aorta

AU - Nebigil, C.

AU - Malik, Kafait

PY - 1992

Y1 - 1992

N2 - This study was performed to characterize the subtype of adrenergic receptor(s) (AR) involved in prostacyclin synthesis [measured as 6-keto- prostaglandin (PG)F(1α)] elicited by AR agonists in cultured vascular smooth muscle cells of rabbit aorta. Both alpha-1 and alpha-2 AR agonists enhanced 6-keto-PGF(1α) synthesis in a dose-dependent manner with the following order of potency: norepinephrine > BHT 933 > UK 14304 > xylazine > phenylephrine ≥ methoxamine > cirazoline. Isoproterenol and oxymetazoline did not alter 6- keto-PGF(1α) synthesis. Methoxamine-induced 6-keto-PGF(1α) synthesis was not reduced by the alpha-2 AR antagonist rauwolscine. The affinities of AR antagonists (PA2 value) in inhibiting methoxamine-induced 6-keto-PGF(1α) synthesis were of the following order: prazosin > WB 4101 > corynanthine > yohimbine. Administration of WB 4101 and the irreversible alpha-1B AR antagonist chloroethylclonidine reduced norepinephrine (in the presence of rauwolscine, 10-8 M)- or methoxamine-induced 6-keto-PGF(1α) synthesis; WB 4101 was more potent than chloroethylclonidine. UK 14304-induced 6-keto- PGF(1α) synthesis was not reduced by chloroethylclonidine or BRL 44408, a selective alpha-2A AR antagonist, but it was inhibited by other alpha AR antagonists. The affinities of AR antagonists (PA2 values) in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis were of the following order: rauwolscine > yohimbine > BAM 1303 > BRL 41992 > WB 4101 > ARC 239 ≥ prazosin > SKF 104078 ≥ corynanthine. The order of affinity of alpha-2 AR antagonists in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis in vascular smooth muscle cells was similar to that derived from radioligand binding studies in opossum kidney cell line receptors classified as alpha-2C receptors. These data suggest that 6-keto-PGF(1α) synthesis elicited by adrenergic stimuli in cultured vascular smooth muscle cells of rabbit aorta is mediated primarily via alpha-2C and to a lesser extent alpha-1A receptors.

AB - This study was performed to characterize the subtype of adrenergic receptor(s) (AR) involved in prostacyclin synthesis [measured as 6-keto- prostaglandin (PG)F(1α)] elicited by AR agonists in cultured vascular smooth muscle cells of rabbit aorta. Both alpha-1 and alpha-2 AR agonists enhanced 6-keto-PGF(1α) synthesis in a dose-dependent manner with the following order of potency: norepinephrine > BHT 933 > UK 14304 > xylazine > phenylephrine ≥ methoxamine > cirazoline. Isoproterenol and oxymetazoline did not alter 6- keto-PGF(1α) synthesis. Methoxamine-induced 6-keto-PGF(1α) synthesis was not reduced by the alpha-2 AR antagonist rauwolscine. The affinities of AR antagonists (PA2 value) in inhibiting methoxamine-induced 6-keto-PGF(1α) synthesis were of the following order: prazosin > WB 4101 > corynanthine > yohimbine. Administration of WB 4101 and the irreversible alpha-1B AR antagonist chloroethylclonidine reduced norepinephrine (in the presence of rauwolscine, 10-8 M)- or methoxamine-induced 6-keto-PGF(1α) synthesis; WB 4101 was more potent than chloroethylclonidine. UK 14304-induced 6-keto- PGF(1α) synthesis was not reduced by chloroethylclonidine or BRL 44408, a selective alpha-2A AR antagonist, but it was inhibited by other alpha AR antagonists. The affinities of AR antagonists (PA2 values) in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis were of the following order: rauwolscine > yohimbine > BAM 1303 > BRL 41992 > WB 4101 > ARC 239 ≥ prazosin > SKF 104078 ≥ corynanthine. The order of affinity of alpha-2 AR antagonists in inhibiting UK 14304-induced 6-keto-PGF(1α) synthesis in vascular smooth muscle cells was similar to that derived from radioligand binding studies in opossum kidney cell line receptors classified as alpha-2C receptors. These data suggest that 6-keto-PGF(1α) synthesis elicited by adrenergic stimuli in cultured vascular smooth muscle cells of rabbit aorta is mediated primarily via alpha-2C and to a lesser extent alpha-1A receptors.

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M3 - Article

VL - 260

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EP - 858

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

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