Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat.
beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. We have employed radioligand binding and cell purification techniques to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-[125I] iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. [125I]iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of [125I]iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types.
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol; D001665:Binding Sites; D002478:Cells, Cultured; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008297:Male; D009206:Myocardium / Q000166:cytology; D010869:Pindolol / Q000031:analogs & derivatives; D011217:Practolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007457:Iodine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C002904:zinterol; D020120:Iodocyanopindolol; D010869:Pindolol; D015784:Betaxolol; D011217:Practolol