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THIRST AND VOLUME, ELECTROLYTE HOMEOSTASIS

Drinking behavior elicited by central injection of angiotensin II: roles for protein kinase C and Ca²⁺/calmodulin-dependent protein kinase II

¹Department of Physiology and Functional Genomics and ²McKnight Brain Institute, University of Florida, Gainesville, Florida 32610

Submitted 25 March 2003 ; accepted in final form 6 May 2003

Prior studies utilizing neurons cultured from the hypothalamus and brain stem of newborn rats have demonstrated that ANG II-induced modulation of neuronal firing involves activation of both protein kinase C (PKC) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). The present studies were performed to determine whether these signaling molecules are also involved in physiological responses elicited by ANG II in the brain in vivo. Central injection of ANG II (10 ng/2 µl) into the lateral cerebroventricle (icv) of Sprague-Dawley rats increased water intake in a time-dependent manner. This ANG II-mediated dipsogenic response was attenuated by central injection of the PKC inhibitors chelerythrine chloride (0.5-50 µM, 2 µl) and Go-6976 (2.3 nM, 2 µl) and by the CaMKII inhibitor KN-93 (10 µM, 2 µl). Conversely, icv injection of chelerythrine chloride (50 µM, 2 µl) and KN-93 (10 µM, 2 µl) had no effect on the dipsogenic response elicited by central injection of carbachol (200 ng/2 µl). Furthermore, injection of ANG II (10 ng/2 µl) icv increases the activity of both PKC- and CaMKII in rat septum and hypothalamus. These data suggest that signaling molecules involved in ANG II-induced responses in vitro are also relevant in physiological responses elicited by ANG II in the whole animal model.

calcium/calmodulin-dependent protein kinase II; intracellular signaling; intracerebroventricular; third cerebroventricle; carbachol

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