Binding and functional characterization of alpha-2 adrenergic receptor subtypes on pig vascular endothelium

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Abstract

Alpha-2 adrenergic receptor subtypes were characterized in membranes of pig vascular endothelium using [3H]rauwolscine. Alpha-2 adrenergic receptor subtypes that mediate endothelium-dependent vascular relaxation were studied in vitro by using ring segments of pig epicardial coronary arteries. Specific [3H]rauwolscine binding in endothelial membranes was saturable and to a single class of high-affinity sites with a mean K(D) of 0.217 ± 0.05 nM and B(max) of 156 ± 28 fmol/mg of protein. Nonlinear regression analysis indicated that competition binding curves for drugs that distinguish the alpha-2A adrenergic receptor subtype from the alpha-2C adrenergic receptor subtype fit best to two-site binding models. K(l) values for drugs in binding to endothelial alpha-2 adrenergic receptors correlated well with their K(l) values for alpha-2A (r = .98) and alpha-2C (r = .97) adrenergic receptor subtypes identified in other tissues. Vascular endothelium contained 23% alpha-2A and 77% alpha-2C adrenergic receptors. In the presence of indomethacin, the rank order of potency for agonists that cause endothelium- dependent vascular relaxation was p-iodoclonidine > clonidine > UK-14,304 > guanabenz > epinephrine > norepinephrine. K(B) values for antagonist inhibition of epinephrine-induced, endothelium-dependent vascular relaxation correlated best with K(l) values for antagonist binding at the alpha-2A adrenergic receptor subtype. These results suggest that the alpha-2A and alpha-2C adrenergic receptor subtypes are present on pig vascular endothelium and that the alpha-2A adrenergic receptor subtype mediates indomethacin- insensitive, endothelium-dependent relaxation of pig epicardial coronary arteries.

Original languageEnglish
Pages (from-to)1126-1133
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number3
StatePublished - 1993

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Adrenergic alpha-2 Receptors
Vascular Endothelium
Swine
Vasodilation
Yohimbine
Indomethacin
Epinephrine
Coronary Vessels
Guanabenz
Membranes
Clonidine
Pharmaceutical Preparations
Adrenergic Receptors
Endothelium
Norepinephrine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Binding and functional characterization of alpha-2 adrenergic receptor subtypes on pig vascular endothelium",
abstract = "Alpha-2 adrenergic receptor subtypes were characterized in membranes of pig vascular endothelium using [3H]rauwolscine. Alpha-2 adrenergic receptor subtypes that mediate endothelium-dependent vascular relaxation were studied in vitro by using ring segments of pig epicardial coronary arteries. Specific [3H]rauwolscine binding in endothelial membranes was saturable and to a single class of high-affinity sites with a mean K(D) of 0.217 ± 0.05 nM and B(max) of 156 ± 28 fmol/mg of protein. Nonlinear regression analysis indicated that competition binding curves for drugs that distinguish the alpha-2A adrenergic receptor subtype from the alpha-2C adrenergic receptor subtype fit best to two-site binding models. K(l) values for drugs in binding to endothelial alpha-2 adrenergic receptors correlated well with their K(l) values for alpha-2A (r = .98) and alpha-2C (r = .97) adrenergic receptor subtypes identified in other tissues. Vascular endothelium contained 23{\%} alpha-2A and 77{\%} alpha-2C adrenergic receptors. In the presence of indomethacin, the rank order of potency for agonists that cause endothelium- dependent vascular relaxation was p-iodoclonidine > clonidine > UK-14,304 > guanabenz > epinephrine > norepinephrine. K(B) values for antagonist inhibition of epinephrine-induced, endothelium-dependent vascular relaxation correlated best with K(l) values for antagonist binding at the alpha-2A adrenergic receptor subtype. These results suggest that the alpha-2A and alpha-2C adrenergic receptor subtypes are present on pig vascular endothelium and that the alpha-2A adrenergic receptor subtype mediates indomethacin- insensitive, endothelium-dependent relaxation of pig epicardial coronary arteries.",
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T1 - Binding and functional characterization of alpha-2 adrenergic receptor subtypes on pig vascular endothelium

AU - Bockman, Charles

AU - Jeffries, W. B.

AU - Abel, Peter W.

PY - 1993

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N2 - Alpha-2 adrenergic receptor subtypes were characterized in membranes of pig vascular endothelium using [3H]rauwolscine. Alpha-2 adrenergic receptor subtypes that mediate endothelium-dependent vascular relaxation were studied in vitro by using ring segments of pig epicardial coronary arteries. Specific [3H]rauwolscine binding in endothelial membranes was saturable and to a single class of high-affinity sites with a mean K(D) of 0.217 ± 0.05 nM and B(max) of 156 ± 28 fmol/mg of protein. Nonlinear regression analysis indicated that competition binding curves for drugs that distinguish the alpha-2A adrenergic receptor subtype from the alpha-2C adrenergic receptor subtype fit best to two-site binding models. K(l) values for drugs in binding to endothelial alpha-2 adrenergic receptors correlated well with their K(l) values for alpha-2A (r = .98) and alpha-2C (r = .97) adrenergic receptor subtypes identified in other tissues. Vascular endothelium contained 23% alpha-2A and 77% alpha-2C adrenergic receptors. In the presence of indomethacin, the rank order of potency for agonists that cause endothelium- dependent vascular relaxation was p-iodoclonidine > clonidine > UK-14,304 > guanabenz > epinephrine > norepinephrine. K(B) values for antagonist inhibition of epinephrine-induced, endothelium-dependent vascular relaxation correlated best with K(l) values for antagonist binding at the alpha-2A adrenergic receptor subtype. These results suggest that the alpha-2A and alpha-2C adrenergic receptor subtypes are present on pig vascular endothelium and that the alpha-2A adrenergic receptor subtype mediates indomethacin- insensitive, endothelium-dependent relaxation of pig epicardial coronary arteries.

AB - Alpha-2 adrenergic receptor subtypes were characterized in membranes of pig vascular endothelium using [3H]rauwolscine. Alpha-2 adrenergic receptor subtypes that mediate endothelium-dependent vascular relaxation were studied in vitro by using ring segments of pig epicardial coronary arteries. Specific [3H]rauwolscine binding in endothelial membranes was saturable and to a single class of high-affinity sites with a mean K(D) of 0.217 ± 0.05 nM and B(max) of 156 ± 28 fmol/mg of protein. Nonlinear regression analysis indicated that competition binding curves for drugs that distinguish the alpha-2A adrenergic receptor subtype from the alpha-2C adrenergic receptor subtype fit best to two-site binding models. K(l) values for drugs in binding to endothelial alpha-2 adrenergic receptors correlated well with their K(l) values for alpha-2A (r = .98) and alpha-2C (r = .97) adrenergic receptor subtypes identified in other tissues. Vascular endothelium contained 23% alpha-2A and 77% alpha-2C adrenergic receptors. In the presence of indomethacin, the rank order of potency for agonists that cause endothelium- dependent vascular relaxation was p-iodoclonidine > clonidine > UK-14,304 > guanabenz > epinephrine > norepinephrine. K(B) values for antagonist inhibition of epinephrine-induced, endothelium-dependent vascular relaxation correlated best with K(l) values for antagonist binding at the alpha-2A adrenergic receptor subtype. These results suggest that the alpha-2A and alpha-2C adrenergic receptor subtypes are present on pig vascular endothelium and that the alpha-2A adrenergic receptor subtype mediates indomethacin- insensitive, endothelium-dependent relaxation of pig epicardial coronary arteries.

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