Open AccessAgonist versus antagonist binding to alpha-adrenergic receptors.
Author(s) -
Brian B. Hoffman,
Thomas Michel,
D. M. Kilpatrick,
Robert J. Lefkowitz,
Margaret E. M. Tolbert,
H R Gilman,
John N. Fain
Publication year - 1980
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.77.8.4569
Subject(s) - receptor , agonist , chemistry , alpha (finance) , endocrinology , adrenergic receptor , glycogen phosphorylase , epinephrine , radioligand , medicine , alpha 2 adrenergic receptor , biochemistry , glycogen , biology , construct validity , nursing , patient satisfaction
The binding properties of two alpha-adrenergic radioligands, [3H]epinephrine (an agonist) and [3H]dihydroergocryptine (an antagonist), were compared in two model systems--membranes derived from human platelets and membranes from rat liver. The platelet contains exclusively alpha 2 and the liver mostly (approximately 80%) alpha 1 receptors. Agonists induce the formation of a guanine nucleotide-sensitive high-affinity state of alpha 2 but not alpha 1 receptors. [3H]Dihydroergocryptine labels all the alpha receptors, whereas [3H]epinephrine at low concentrations labels predominantly the high-affinity form of the alpha 2 receptor in both platelet and liver. However, in the liver, alpha-adrenergic effects such as glycogen phosphorylase activation are shown to be mediated via alpha 1 receptors. Thus, in liver membranes the endogenous "physiological" agonist may not label the physiologically relevant alpha 1 receptors in typical radioligand binding assays using low concentrations of [3H]epinephrine.
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