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Nitric oxide (NO) negatively modulates the secretion of vasopressin (AVP), oxytocin (OT) and atrial natriuretic peptide (ANP) induced by the increase in extracellular osmolality, whereas carbon monoxide (CO) and hydrogen sulphide (H 2 S) act to potentiate it; however, little information is available for the osmotic challenge model about whether and how such gaseous systems modulate each other. Therefore, using an acute ex vivo model of hypothalamic and neurohypophyseal explants (obtained from male 6/7-week-old Wistar rats) under conditions of extracellular iso-and hypertonicity, we determined the effects of NO (600 μmol L -1 sodium nitroprusside), CO (100 μmol L -1 tricarbonylchloro[glycinato]ruthenium [II]) and H 2 S (10 mmol L -1 sodium sulphide) donors and nitric oxide synthase (NOS) (300 μmol L -1 N ω -methyl-l-arginine [LNMMA]), haeme oxygenase (HO) (200 μmol L -1 Zn(II) deuteroporphyrin IX 2,4-bisethylene glycol [ZnDPBG]) and cystathionine β-synthase (CBS) (100 μmol L -1 aminooxyacetate [AOA]) inhibitors on the release of hypothalamic ANP and hypothalamic and neurohypophyseal AVP and OT, as well as on the activities of NOS, HO and CBS. LNMMA reversed hyperosmolality-induced NOS activity, and enhanced hormonal release by the hypothalamus and neurohypophysis, in addition to increasing CBS and hypothalamic HO activity. AOA decreased hypothalamic and neurohypophyseal CBS activity and hormonal release, whereas ZnDPBG inhibited HO activity and hypothalamic hormone release; however, in both cases, AOA did not modulate NOS and HO activity and ZnDPBG did not affect NOS and CBS activity. Thus, our data indicate that, although endogenous CO and H 2 S positively modulate AVP, OT and ANP release, only NO plays a concomitant role of modulator of hormonal release and CBS activity in the hypothalamus and neurohypophysis and that of HO activity in the hypothalamus during an acute osmotic stimulus, which suggests that NO is a key gaseous controller of the neuroendocrine system. K E Y W O R D S atrial natriuretic peptide, carbon monoxide, hydrogen sulphide, nitric oxide, oxytocin, vasopressin 2 of 16 | COLETTI ET aL. | INTRODUC TI ONThe release of vasopressin (AVP) and oxytocin (OT) by the hypothalamus and the neurohypophysis is a very complex and robust process that is controlled by many factors produced both within and outside these brain sites. 1 Among such factors, atrial natriuretic peptide (ANP) stands out as established modulator of thirst and AVP release, 2-4 whereas a novel class of small polar molecules, mainly represented by nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H 2 S), 5 have achieved prominence more recently.NO is produced from the amino acid l-arginine via a reaction catalysed by the enzyme nitric oxide synthase (NOS), which presents three major isoforms (neuronal [nNOS], endothelial [eNOS] and inducible [iNOS]), where, in the central nervous system (CNS), nNOS is considered the main isoform. 6 NOS active form is usually dimeric and exhibits an oxygenase domain, in which, in addition to ...

17β-Estradiol (E2) has been shown to modulate the renin–angiotensin system in hydromineral and blood pressure homeostasis mainly by attenuating angiotensin II (ANGII) actions. However, the cellular mechanisms of the interaction between E2 and angiotensin II (ANGII) and its physiological role are largely unknown. The present experiments were performed to better understand the interaction between ANGII and E2 in body fluid control in female ovariectomized (OVX) rats. The present results are the first to demonstrate that PKC/p38 MAPK signaling is involved in ANGII-induced water and sodium intake and oxytocin (OT) secretion in OVX rats. In addition, previous data from our group revealed that the ANGII-induced vasopressin (AVP) secretion requires ERK1/2 signaling. Therefore, taken together, the present observations support a novel concept that distinct intracellular ANGII signaling gives rise to distinct neurohypophyseal hormone release. Furthermore, the results show that E2 attenuates p38 MAPK phosphorylation in response to ANGII but not PKC activity in the hypothalamus and the lamina terminalis, suggesting that E2 modulates ANGII effects through the attenuation of the MAPK pathway. In conclusion, this work contributes to the further understanding of the interaction between E2 and ANGII signaling in hydromineral homeostasis, as well as it contributes to further elucidate the physiological relevance of PKC/p38 MAPK signaling on the fluid intake and neurohypophyseal release induced by ANGII.

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacologic dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food and water intakes. Blockade of Gpr160 in the 4V, independent of pharmacologic CART treatment, caused an increase in both overnight food and water intakes. The decrease in food, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a GLP-1 receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and non-neuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection, and extend these findings to water drinking. Gpr160ir was observed in both neuronal and non-neuronal cell types in regions known to be important in the multiple pharmacologic effects of CARTp, identifying those areas as targets for future compromise of function studies.