mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II. Endocrinology 2016 08;157(8):3140-8
Date
06/03/2016Pubmed ID
27254006Pubmed Central ID
PMC4967111DOI
10.1210/en.2016-1243Scopus ID
2-s2.0-84982797786 7 CitationsAbstract
Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1-7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.
Author List
Muta K, Morgan DA, Grobe JL, Sigmund CD, Rahmouni KAuthors
Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of WisconsinCurt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Blood Pressure
Brain
Drinking
Drinking Behavior
Female
Injections, Intraventricular
Male
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Inbred C57BL
Mice, Transgenic
Multiprotein Complexes
Signal Transduction
TOR Serine-Threonine Kinases
