Modulation of the delayed rectifier K+ current in neurons by an angiotensin II type 2 receptor fragment
Kang, J.; Richards, E.M.; Posner, P.; Sumners, C.
American Journal of Physiology 268(1 Pt 1): C278-C282
1995
ISSN/ISBN: 0002-9513 PMID: 7840157 Document Number: 447706
Angiotensin II (ANG II) stimulates the delayed rectifier K+ current (I-K) in neurons cultured from rat hypothalamus and brain stem via AT-2 receptors, and this effect involves activation of a G-i protein and protein phosphatase 2A (PP2A). However, there was no evidence that the AT-2 receptor involved in this response was the same as the recently cloned AT-2 receptor. In the present study, intracellular injection of a 22-amino acid peptide (PEP-22) corresponding to the putative third intracellular loop of the cloned AT-2 receptor elicited an increase in I-K in cultured neurons that was similar to the effect produced by ANG II. Furthermore, this effect of PEP-22 was abolished by pertussis toxin (200 ng/ml, 24 h) pretreatment and also by superfusion of the PP2A inhibitor okadaic acid (10 nM), suggesting the involvement of G-i protein and PP2A, respectively. Intracellular injection of a random peptide or normal pipette solution did not affect neuronal I-K. This is direct evidence to link the cloned AT-2 receptor to a defined response elicited by ANG II.