European Journal of Pharmacology, 140 (1987) 1-11 1 Elsevier EJP 00841 The distribution of fl-adrenoceptors in dog kidney: an autoradiographic analysis Robert Lew and Roger J. Summers * Department of Pharmacology, Universityof Melbourne, Parkville, 3052, Australia Received7 April 1987, accepted5 May 1987 The distribution of fl-adrenoceptors in slide-mounted dog kidney sections was determined using the radioligand (-)-[125I]cyanopindolol ((-)-[125I]CYP) and autoradiography. Using conditions designed to prevent (-)-[12SI]CYP binding to non-fl-adrenoceptor sites, biochemical studies revealed that (-)-[~25 I]CYP binding equilibrated within 150 rain (K 1 = 3.2 × 108 M -1 rain-l), was saturable (K D = 30.72 +_2.96 pM; Bm~x = 0.57 +_ 0.03 fmol/section, n = 4) and stereoselective with respect to the stereoisomers of propranolol and pindolol. Delineation of fl-adrenoceptor subtypes with the selective flx-adrenoceptor antagonist betaxolol and fl2-adrenoceptor antagonist ICI 118,551 demonstrated that the proportions of fix" : fl2-adren°cep tors was between 1 : 6 and 1 : 11. Autoradiographic studies showed that fl~-adren- oceptors were localized on the juxtaglomemlar apparatus and glomeruli, while fl2-adrenoceptors were localized on medullary rays. The distribution of/3-adrenoceptors with respect to renal function in the dog kidney is discussed. fl-Adrenoceptors; Kidney; Autoradiography; (-)-[125I]Cyanopindolol; (Dog) 1. Introduction Morphological studies have shown that the mammalian kidney is innervated by sympathetic nerves which are closely associated with vascular and tubular structures in rat, monkey and dog kidney (McKenna and Angelakos, 1968; Barajas, 1978; DiBona, 1977). Stimulation of these nerves releases noradrenaline to activate a- and fl-adren- oceptors and mediate changes in renal haemo- dynamics, sodium and water reabsorption, glomerular filtration rate, renin release and prob- ably release of hormones such as erythropoietin (for review see Insel and Snavely, 1981; DiBona, 1982). The role of fl-adrenoceptors in renal func- tion has been extensively investigated. In dog kid- ney, renin release from the juxtaglomerular ap- paratus is mediated by fl-adrenoceptors since the increase in release after renal nerve stimulation is * To whom all correspondenceshould be addressed. abolished by the fl-adrenoceptor antagonist pro- pranolol and occurs in the absence of changes to either blood flow or glomerular filtration rate. Selective fll-adrenoceptor antagonists but not fl2- adrenoceptor antagonists inhibit noradrenaline- stimulated renin release (Kopp et al., 1980; Himori et al., 1980; Osborn et al., 1981) while similar observations have also been made in rat kidney (Oates et al., 1978; Nakane et al., 1980; Churchill et al., 1983). fl-Adrenoceptors do not appear to play a role in control of renal blood flow (Zambraski et al., 1978). In dog kidney, renal nerve stimulation activates al-adrenoceptors to produce vaso- constriction (Hisa et al., 1985). Although pretreat- ment with phenoxybenzamine or prazosin abolishes the a-adrenoceptor-mediated vaso- constriction, fl-adrenoceptor-mediated vasodila- tation is not observed (Zambraski et al., 1978; Holdaas and DiBona, 1984) as in other vascular beds (Taira et al., 1977). 0014-2999/87/$03.50 © 1987 Elsevier SciencePublishers B.V. (BiomedicalDivision)