CGP 42112;NΑ-NICOTINOYL-TYR-(NΑ-CBZ-ARG)-LYS-HIS-PRO-ILE

CGP-42112 (≥1 nM) significantly inhibits cGMP production from the basal value. CGP-42112 (≥1 nM) significantly inhibits TH-enzyme activity from the basal value. These inhibitory effects of CGP-42112 on TH-enzyme activity and-cGMP production are abolished by PD123319 (AT(2)-R antagonist) while CV-11974 (AT(1)-R antagonist) is ineffective. [ ¹²⁵ I]CGP-42112 binds selectively to the AT2 angiotensin II receptor subtype. [ ¹²⁵ I]CGP-42112 binds with higher affinity in the brain than in the adrenal. beta-Mercaptoethanol enhanced [ ¹²⁵ I]CGP-42112 binding in the brain, but does not alter its binding in the adrenal. [ ¹²⁵ I]CGP-42112 binds with high affinity (Kd = 0.07-0.3 nM, depending on the area studied). [ ¹²⁵ I]CGP-42112 binding is selective for AT2 receptors, as determined by lack of competition with the AT1 ligand losartan, and competition by the AT2 ligands PD 123177 and unlabeled CGP-42112 and the non-selective peptides Ang II and angiotensin III (Ang III).

Intravenous infusions of CGP-42112 (0.1 and 1 mg kg-1 min-1) and PD 123319 (0.36 and 1 mg kg-1 min-1) shifted the upper limit of CBF autoregulation toward higher blood pressures without affecting baseline CBF.