PHARMACOLOGICAL CHARACTERIZATION OF ANGIOTENSIN-II AT(2) RECEPTOR SUBTYPE HETEROGENEITY IN THE RAT ADRENAL-CORTEX AND MEDULLA

Adrenal angiotensin II (AII) receptors have been pharmacologically and structurally divided into two main subtypes, AT(1) and AT(2). Radioli gand receptor binding assays with I-125-sarcosine(1), isoleucine(8) an giotensin II (I-125-SI AII) in the presence of losartan, an AT(1) sele ctive ligand, and PD123177 an AT(2) selective ligand, indicated that t he AT(1) subtype was predominant in membrane homogenates of the rat ad renal cortex (AT(1) Bmax = 649 +/- 62 fmol/mg protein; AT(2) Bmax = 23 7 +/- 29 fmol/mg protein). In membrane homogenates of the adrenal medu lla, the AT(2) subtype was predominant (AT(1) Bmax = 55 +/- 5 fmol/mg protein; AT(2) Bmax = 109 +/- 29 fmol/mg protein). Overall 58% of the I-125-SI AII binding in the rat adrenal was to the AT(1) subtypes, and 42% was to the AT(2) subtypes. The outer cortex contained 59% of the AII receptor binding sites in the adrenal, while the medulla accounted for the remaining 41%. The affinity of the AT(1) binding sites in mem brane homogenates of the cortex and medulla (K-D = 672 +/- 123 pM and 573 +/- 85 pM, respectively) was not significantly different. The affi nity for I-125-SII AII of AT(2) binding sites in membrane homogenates was higher than that of AT(1) binding sites. The affinity for I-125-SI AII of AT(2) binding sites in membrane homogenates of the outer corte x (K-D = 265 +/- 35 pM) was significantly less than that in the medull a (K-D = 133 +/- 11 pM). In vitro receptor autoradiography also demons trated that the AT(2) subtype in frozen sections of the cortex had a l ower affinity (K-D = 1512 +/- 191 pM) than that in the medulla (K-D = 867 +/- 72 pM) The heterogeneous affinity of adrenal AT(2) binding sit es may indicate existence of multiple AT(2) receptor subtypes in the r at adrenal.