Adrenergic receptors in human liver plasma membranes: predominance of beta 2- and alpha 1-receptor subtypes.
Adrenergic receptors in human liver plasma membranes were characterized by radioligand binding assays. The binding of [3H]dihydroalprenolol [( 3H]DHA) to partially purified membranes was rapid, of high affinity, saturable, and stereospecific. The binding of [125I]iodocyanopindolol to the same membranes was also saturable and stereospecific, but extremely slow, and at 37 C required about 6 h for equilibration. The maximum number of binding sites from six livers determined with these two beta-receptor ligands was 36-83 fmol/mg protein. Catecholaminergic agonists competed for these binding sites in the order typical for beta 2-adrenergic receptors. IPS 339 [(tertiarybutylamino-3-ol-2-propyl)oximino-9-fluorene hydrochloride], a beta 2-selective antagonist, was at least 3 orders of magnitude more potent in inhibiting the binding of [3H]DHA than the beta 1-antagonist, atenolol. Computer-aided analysis of the competition curves as well as Hofstee transformations of the binding data indicated the predominance of the beta 2-subtype. The GTP analog guanyl-5'-yl-imidodiphosphate, decreased the binding affinity of the agonist, l-isoproterenol, indicating the modulation of agonist-promoted coupling of the receptors to guanine nucleotide regulatory proteins. The maximum number of binding sites for the binding of [3H]prazosin and [3H]dihydroergocryptine were the same (60-70 fmol/mg protein), indicating that the majority of the alpha-receptors are of the alpha 1-subtype. Competition experiments with prazosin and yohimbine confirmed the predominance of the alpha 1-receptor subtype, although the presence of alpha 2-receptors cannot be completely ruled out. These results indicate that adrenergic receptors in human liver plasma membranes are predominantly of the beta 2- and alpha 1-subtypes.
D000368:Aged; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D020120:Iodocyanopindolol; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013565:Sympatholytics / Q000378:metabolism; D013566:Sympathomimetics / Q000378:metabolism; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics; D013566:Sympathomimetics; D004088:Dihydroergotoxine; D015016:Yohimbine; D006165:Guanylyl Imidodiphosphate; D004082:Dihydroalprenolol; D020120:Iodocyanopindolol; D010869:Pindolol; D011224:Prazosin