In bovine adrenal medullary cells synergistically acting type 1 and type 2 angiotensin II (AII) receptors activate the fibroblast growth factor-2 (FGF-2) gene through a unique AII-responsive promoter element. Both the type 1 and type 2 AII receptors and the downstream cyclic adenosine 1',3'-monophosphate- and protein kinase C-dependent signaling pathways activate the FGF-2 promoter through a novel signal-transducing mechanism. This mechanism, which we have named integrative nuclear FGF receptor-1 signaling, involves the nuclear translocation of FGF receptor-1 and its subsequent transactivation of the AII-responsive element in the FGF-2 promoter.

Angiotensin and mineralocorticoids, the hormones of sodium conservation, acted together to arouse a sodium appetite with shorter latency and greater magnitude than is produced by larger amounts of each acting alone. This potentiation was selective for sodium ingestion and occurred in the absence of significant changes in sodium balance. Therefore, because endogenous angiotensin and mineralocorticoids are concurrently elevated during sodium deficiency, sodium appetite may be aroused by a synergy of the peptide and the steroid.

Together, the data imply that adrenal steroids, in addition to acting through classic cytosolic receptors, may also act on membrane receptor systems, producing rapid changes in behavior.

Central injections of angiotensin II (AngII) increase both water and NaCl intake. These effects of AngII occur largely through stimulation of the AngII type 1 (AT(1)) receptor. Stimulation of the AT(1) receptor leads to a number of intracellular events, including phospholipase C (PLC) activation and the subsequent formation of diacylglycerol and inositol trisphosphate (IP(3)), which then activate protein kinase C (PKC) and increase intracellular calcium, respectively. In addition, AT(1) receptor stimulation leads to the activation of MAPK family members. Recent experiments using mutated AT(1) receptor constructs or the AngII analog Sar(1),Ile(4),Ile(8)-AngII (SII) revealed that MAPK activation can occur independent of PLC/PKC/IP(3) activation. The present experiments used in vitro and in vivo approaches to clarify the cellular and behavioral responses to SII. Specifically, SII mimicked AngII stimulation of MAPK in AT(1) receptor-transfected COS-1 cells and rat brain but blocked the effects of AngII in two distinct settings: in vitro stimulation of IP(3) and in vivo increases in water intake. Moreover, SII increased intake of 1.5% NaCl, despite the SII blockade of IP(3) formation and water intake. Examination of brain tissue showed increases in Fos expression in several AngII-sensitive brain areas after injection of AngII, but not SII. The lack of SII-induced IP(3) production, water intake, and Fos expression strongly suggest that the PLC/PKC/IP(3) pathway is required for water intake, but not NaCl consumption stimulated by AngII. Collectively, these results support the hypothesis that divergent intracellular signals from a single receptor type can give rise to separable behavioral phenomena.

No abstract