Document Type
Article
Publication Date
10-2-2014
Publication Title
Brain Research
Keywords
AT(1) angiotensin receptors, Angiotensin, Brain, Desensitization, Hypertension, Radioligand, Saline intake, Thirst, Water intake
ISSN
0006-8993
Volume
1583
First Page
132
Last Page
40
Abstract
Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To test this hypothesis, we examined the binding of a radiolabeled agonist ((125)I-sarcosine(1) Ang II) and a radiolabeled antagonist ((125)I-sarcosine(1), isoleucine(8) Ang II) in brain homogenates and tissue sections prepared from rats given repeated injections of Ang II or vehicle. Although no treatment-related differences were found in hypothalamic homogenates, a focus on specific brain structures using receptor autoradiography, found that the desensitization treatment reduced binding of both radioligands in the paraventricular nucleus of the hypothalamus (PVN) and median preoptic nucleus (MnPO), but not in the subfornical organ (SFO). Because G protein coupling is reported to have a selective effect on agonist binding without affecting antagonist binding, these findings do not support a G protein uncoupling treatment effect. This suggests that receptor number is more critical to the water intake response than the saline intake response, or that pathways downstream from the G protein mediate desensitization of the water intake response.
NSUWorks Citation
Speth, Robert C.; Vento, Peter J.; Carrera, Eduardo J.; Gonzalez-Reily, Luz; Linares, Andrea; Santos, Kira; Swindle, Jamala D.; and Daniels, Derek, "Acute repeated intracerebroventricular injections of angiotensin II reduce agonist and antagonist radioligand binding in the paraventricular nucleus of the hypothalamus and median preoptic nucleus in the rat brain" (2014). HPD Articles. 68.
https://nsuworks.nova.edu/hpd_facarticles/68
ORCID ID
0000-0002-6434-2153
DOI
10.1016/j.brainres.2014.07.053
Copyright
Copyright © 2014 Elsevier B.V. All rights reserved.
