DIFFERENTIAL EFFECT OF DITHIOTHREITOL AND DUP-753 ON ANGIOTENSIN-II RECEPTOR SUBTYPES IN BOVINE CEREBELLAR CORTEX

Angiotensin II (AII) receptor subtypes were investigated in bovine cer ebellar cortical membranes (BCCM) using agonists and antagonists. Diff erences were observed whether the tissue for the characterization was used fresh or frozen. In fresh BCCM, AII and angiotensin III (AIII) (n ot selective), p-aminophenylalanine6-AII ([pNH2Phe6]AII) (AT2 selectiv e), and DuP 753 (AT1 selective) interacted with two sites, at high and low affinity. In the presence of 10 mM dithiothreitol (DTT), the low- affinity site for AIII and [pNH2Phe6]AII and the high-affinity site fo r DuP 753 were no longer detectable. The same effect was obtained with 1 muM DuP 753, with only the low-affinity component of [pNH2Phe6]AII being resistant to this blocker. In frozen BCCM, DuP 753, PD 123319 (A T2 selective), and sarcosine1, isoleucine8-AII ([Sar1Ile8] All) yielde d monophasic curves. These data confirm the presence of multiple recep tors (AT1 and AT2) for AII on BCCM and suggest the possibility that wi thin the AT2 receptors, one subtype, DTT sensitive, may exist. Alterna tively, a heterogeneity in the AT1 class, with respect to the sensitiv ity to DuP753, may be considered.