Identification of a homogeneous class of beta 2-adrenoceptors in human platelets by (-)-125I-iodopindolol binding.
The highly specific beta-adrenoceptor radioligand (-)-125I-iodopindolol (IPIN) was used to label in membranes from human platelets beta-adrenoceptors. Binding of IPIN was at 25 degrees C saturable (Bmax = 7.4 +/- 2.5 fmoles bound/mg protein, N = 10) of high affinity (KD-value = 34.8 +/- 3.3 pM, N = 10), rapid and reversible. beta-Adrenoceptor antagonists inhibited binding of IPIN with monophasic displacement curves and pseudo Hill coefficients (nH) not significantly different from 1.0. The beta 2-selective antagonist ICI 118,551 was much more potent in inhibiting IPIN binding than the beta 1-selective antagonist bisoprolol. IPIN binding was stereospecific as indicated by the 100-times greater potencies of (-)-alprenolol and (-)-isoprenaline in inhibiting binding than their (+)-isomers. beta-Adrenoceptor agonists inhibited binding with slightly shallow displacement curves and nH-values of 0.85-0.88; the order of potency was: isoprenaline greater than adrenaline greater than noradrenaline. These results demonstrate that IPIN labels (in human platelet membranes with high affinity) a homogeneous population of beta 2-adrenoceptors with low capacity.
Wang
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Brodde
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D000262:Adenylyl Cyclases / Q000097:blood; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010869:Pindolol / Q000031:analogs & derivatives* / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C029247:3-iodopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases