Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein.
Angiotensin II (ANG II) elicits an ANG II type 2 (AT2) receptor-mediated increase in outward K+ current (IK; delayed rectifier K+ current) in neurons cocultured from rat hypothalamus and brain stem. Here we have shown that the AT2-receptor-mediated stimulation of neuronal IK 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-Gi alpha, 1:200). Antibodies against other GTP binding proteins (anti-Go alpha, 1:50 and 1:200; anti-Gq/11 alpha, 1:200) did not alter the AT2-receptor-mediated stimulation of neuronal IK 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 (Gi and PP2A) of the signal transduction pathway that is responsible for the AT2-receptor-mediated stimulation of neuronal K+ currents.
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610-0274.
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J
Kang
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Posner
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Sumners
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004594:Electrophysiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000502:physiology; D011188:Potassium / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*
D004988:Ethers, Cyclic; D011945:Receptors, Angiotensin; D019319:Okadaic Acid; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D019204:GTP-Binding Proteins; D011188:Potassium