title: Homogeneous class of beta-1 adrenergic receptors in rat kidney. Identification by (+/-)-125 iodocyanopindolol binding.
abstract: The highly specific beta-adrenergic radio-ligand (+/-)-125 iodocyanopindolol (ICYP) was used to characterize the beta-adrenergic receptor subtype present in rat kidney. Binding of ICYP to membranes from rat kidney was of high affinity (KD = 68.9 pM) and saturable with 1.06 pmoles ICYP bound/g tissue wet wt at maximal occupancy of the sites. Analysis of inhibition of ICYP binding by beta 1- and beta 2-selective adrenergic drugs via pseudo-Scatchard ("Hoifstee') plots resulted in linear plots indicating the existence of a homogeneous population of beta-adrenergic receptors. From the resulting KD-values for practolol (2.2 microM), metoprolol (0.21 microM), zinterol (0.4 microM) and IPS 339 (0.046 microM) it is concluded that the beta-adrenergic receptor in rat kidney is of the beta 1-subtype. This subclassification is further supported by the fact that (-)-noradrenaline and (-)-adrenaline were equipotent in inhibiting ICYP binding. The beta-adrenergic agonists (-)-isoprenaline and zinterol bind to two distinct states of this beta 1-receptor, a high and low affinity state. GTP (10(-4) M) converts this heterogeneous binding into a homogeneous low affinity binding.
mesh_terms: D000818:Animals; D006160:Guanosine Triphosphate / Q000494:pharmacology; D020120:Iodocyanopindolol; D007668:Kidney / Q000032:analysis*; D008024:Ligands; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000032:analysis*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism
chemical_list: D008024:Ligands; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D006160:Guanosine Triphosphate; D010869:Pindolol