Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein
Kang, J.; Posner, P.; Sumners, C.
American Journal of Physiology 267(5 Pt 1): C1389-C1397
1994
ISSN/ISBN: 0002-9513 PMID: 7977700 Document Number: 434395
Angiotensin II (ANG II) elicits an ANG II type 2 (AT-2) receptor-mediated 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 pertussis toxin (PTX; 200 ng/ml) and by intracellular application of an antibody against the inhibitory guanine nucleotide (GTP) binding protein (anti-G-ialpha, 1:200). Antibodies against other GTP binding proteins (anti-G-oalpha, 1:50 and 1:200; anti-G-q/11alpha, 1:200) did not alter the AT-2-receptor-mediated stimulation of neuronal I-K by ANG II (100 nM). Furthermore, this effect of ANG II (100 nM) was inhibited by the serine/threonine phosphatase inhibitor okadaic acid (1-10 nM) and by anti-type 2A protein phosphatase (PP2A) antibodies but not by the tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). Thus we have identified key components (G-i and PP2A) of the signal transduction pathway that is responsible for the AT-2-receptor-mediated stimulation of neuronal K+ currents.