Nonadrenergic imidazoline binding sites on human platelets
Human platelets are shown to possess at least two high-affinity, imidazol(in)e-preferring binding sites that are pharmacologically distinct from alpha-2 adrenoceptors. These nonadrenergic sites were radiolabeled even in the presence of a 10 microM norepinephrine mask of alpha-2 adrenoceptors. Hetero...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 267; no. 3; pp. 1493 - 1502 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.12.1993
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Subjects | |
Online Access | Get full text |
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Summary: | Human platelets are shown to possess at least two high-affinity, imidazol(in)e-preferring binding sites that are pharmacologically
distinct from alpha-2 adrenoceptors. These nonadrenergic sites were radiolabeled even in the presence of a 10 microM norepinephrine
mask of alpha-2 adrenoceptors. Heterogeneity at the nonadrenergic sites was demonstrated by comparing [3H]idazoxan (IDX) binding
vs. [125I]p-iodoclonidine (PIC) binding. Nonadrenergic [125I]PIC-labeled sites were enriched in platelet plasma membranes,
whereas the nonadrenergic sites labeled by [3H] IDX were codistributed between plasma and internal membranes (nonadrenergic
[125I]PIC-labeled sites had Bmax = 62 fmol/mg in plasma membranes and 20 fmol/mg in internal membranes vs. the [3H]IDX-labeled
sites had Bmax = 141 fmol/mg in plasma membranes and 192 fmol/mg in internal membranes). Furthermore, competition binding
studies in the presence of a 10 microM norepinephrine mask revealed major (approximately 75%) and minor (approximately 25%)
binding components on plasma membranes for [125I]PIC. Affinities for the major nonadrenergic [125I]PIC binding site were highly
comparable to human subtype-I1 imidazol(in)e receptor sites in the brain stem (rank order: moxonidine > clonidine > cirazoline
> IDX > amiloride). However, the minor component of [125I]PIC binding was similar to a site reported in kidney, having low
affinities for all compounds tested, except guanabenz. Finally, a third nonadrenergic internal membrane site, labeled by [3H]IDX,
was consistent with a subtype-I2 imidazol(in)e receptor site (rank order: cirazoline > IDX > amiloride > moxonidine > clonidine).
Thus, based on differential subcellular distributions and affinity constants, human platelets appear to possess imidazoline
receptors (subtype-I1 imidazol(in)e receptor and subtype-I2 imidazol(in)e receptor), plus a novel guanabenz-sensitive site,
as well as an alpha-2A adrenoceptor. These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties
previously ascribed to clonidine and endogenous clonidine-displacing substance(s), and may serve as markers of imidazoline
receptors in humans. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |