title: Quantitative comparison of bromoacetylated derivatives of alprenolol and pindolol on beta-adrenergic receptor binding and mobility in S49 cells.
abstract: The reactivities with beta-adrenergic receptors of the bromoacetyl derivatives of the beta-adrenergic antagonists alprenolol and pindolol, BAAM and BIM, respectively, were compared in intact S49 mouse lymphoma cells. Both compounds caused irreversible blockade of receptors and changes in the mobility of the remaining non-modified receptors. BIM proved to be an irreversible blocker of high potency, with an IC50 of 40-60 nM at 4 degrees C, whereas the IC50 for BAAM was 600-900 nM. Moreover, treatment with both compounds resulted in an inhibition of internalization of non-modified receptors (IC50 = 200-300 nM for both). After treatment of desensitized cells which have internalized 50-60% of their surface receptors, with BIM or BAAM, receptor reappearance was found to be slowed down (IC50 about 100 nM for both compounds). The effects of the bromoacetylated antagonists on receptor internalization were apparently selective for beta-adrenergic receptors, since binding and internalization of transferrin or low-density lipoprotein were not affected.
authors.affiliation: Departement Forschung, Kantonsspital, Basel, Switzerland.
authors.forename: R J
authors.initials: RJ
authors.lastname: Box
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D000081005:Cyclohexane Monoterpenes; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000319:Adrenergic beta-Antagonists; D000081005:Cyclohexane Monoterpenes; D008077:Lipoproteins, LDL; D011943:Receptors, Adrenergic, beta; D014168:Transferrin; C057316:N(8)-bromoacetyl-N(1)-3'-(4-indolyloxy)-2'-hydroxypropyl-1,8-diamino-4-menthane; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D010869:Pindolol