ANGIOTENSIN-II TYPE-2 RECEPTOR STIMULATION OF NEURONAL K-BINDING PROTEIN( CURRENTS INVOLVES AN INHIBITORY GTP)

Angiotensin II (ANG II) elicits an ANG II type 2 (AT(2)) receptor-medi ated increase in outward K+ current (I-K; delayed rectifier K+ current ) in neurons cocultured from rat hypothalamus and brain stem. Here we have shown that the AT(2)-receptor-mediated stimulation of neuronal I- K by ANG II (100 nM) was abolished by pretreatment of cultures with pe rtussis toxin (PTX; 200 ng/ml) and by intracellular application of an antibody against the inhibitory guanine nucleotide (GTP) binding prote in (anti-G(i alpha), 1:200). Antibodies against other GTP binding prot eins (anti-G(o alpha), 1:50 and 1:200; anti-G(q/11 alpha), 1:200) did not alter the AT(2)-receptor-mediated stimulation of neuronal I-K by A NG II (100 nM). Furthermore, this effect of ANG II (100 nM) was inhibi ted by the serine/threonine phosphatase inhibitor okadaic acid (1-10 n M) and by anti-type 2A protein phosphatase (PP2A) antibodies but not b y the tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). Thus we have identified key components (G(i) and PP2A) of the signal trans duction pathway that is responsible for the AT(2)-receptor-mediated st imulation of neuronal K+ currents.