CHARACTERIZATION AND LOCALIZATION OF ATYPICAL BETA-ADRENOCEPTORS IN RAT ILEUM

1 Homogenate binding studies and receptor autoradiography have been us ed to examine the binding characteristics and localization of proprano lol-resistant (-)-[I-125]-cyanopindolol (CYP) binding sites in rat ile um. 2 Saturation studies with (-)-[I-125]-CYP and homogenates of rat i leum identified a site with pK(D) 8.89+/-0.08 and B-max=50.3+/-4.1 fmo l mg(-1) protein (n=6). Both beta(1)- and beta(2)-adrenoceptors (AR) w ere not detected in these preparations. 3 (-)-Isoprenaline infusion (4 00 mu g kg(-1) h(-1)) for 14 days caused no significant change in the density of (-)-[I-125]-CYP binding which was 48.9+/-12.8 and 40.6+/-12 .3 fmol mg(-1) protein in control and isoprenaline-treated animals res pectively (n=6) (P=0.97). 4 Competition for (-)-[I-125]-CYP binding in the presence of 0.1 mu M (-)-propranolol gave affinity values for CYP , tertatolol, alprenolol, ICI 118551 and CGP 20712A that correspond to known affinities at atypical beta-ARs. Stereoselectivity ratios for t ertatolol and alprenolol were low. 5 Autoradiographic localization of propranolol resistant (-)-[I-125]-CYP binding showed sites associated with the mucosa and to a lesser extent to the muscularis. A small popu lation of beta(2)-ARs were detected located predominantly in the longi tudinal and circular smooth muscle layers. 6 This study identifies an (-)-[I-125]-CYP binding site in rat ileum that is resistant to blockad e by propranolol (0.1 mu M), is located predominantly in the mucosa, s hows resistance to downregulation by isoprenaline and has binding char acteristics of the atypical beta-AR.