Control of Salivary Secretion by Nitric Oxide and Its Role in Neuroimmunomodulation

Abstract: In many in vivo systems exposure to endotoxins (LPS) leads to the co‐induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), which is important to the regulation of the function of different systems during infection. In submandibular glands (SMG) neural (n)NOS is localized in neural terminals and in striated, granular convoluted and excretory ducts, endothelial (e) NOS in vascular endothelium and ducts, and iNOS in macrophages and in tubules and ducts. In normal adult male rats, injection of an inhibitor of NOS decreased the stimulated salivary secretion and a donor of NO potentiated it, indicating that NO exerts a stimulatory role. A single high dose of LPS (5 mg/kg, i.p.) induced an increase in NOS activity measured by the 14C‐citrulline method, increased PGE content almost 100% as measured by RIA, and blocked stimulated salivary secretion. The administration of a specific iNOS inhibitor, aminoguanidine (AG), with LPS not only decreased NOS activity but significantly decreased PGE content, indicating that NO triggered the activation of COX‐2. LPS increased conversion of labeled arachidonate to prostaglandins (PGs) showing that COX was induced. Since a PGE1 analogue blocked stimulated salivation, the LPS‐induced inhibition of salivation is probably due to release of PGs. Therefore, the use of inhibitors of iNOS and COX‐2 could be very useful to increase salivation during infection since saliva has antimicrobial actions.Fil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Lomniczi, A.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Elverdín, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Suburo, Angela Maria. Universidad Austral; ArgentinaFil: Faletti, Alicia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: McCann, Samuel M.. State University of Louisiana; Estados Unido

Posible efecto de los canabinoides endógenos y el rimonabant sobre la insulinorresistencia y la función de las células β

El propósito del trabajo es estudiar el posible papel regulador del sistema canabinoide sobre la secreción de insulina y los cambios endocrino-metabólicos inducidos en ratas normales por una dieta rica en fructosa (DRF).Facultad de Ciencias Médicas (FCM

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Mifepristone, a Blocker of Glucocorticoid Receptors, Promotes Photoreceptor Death

PURPOSE. Glucocorticoids are best known by their protective effect on retinal photoreceptor damage. However, they could also be involved in photoreceptor homeostasis under basal, nonstressful conditions. Therefore, we aimed to study glucocorticoid-induced changes of survival-related molecules in male mice retinas under standard illumination conditions (12 hours light, 60 lux/12 h dark). METHODS. Male Balb-c mice were injected with dexamethasone (DEX), a selective glucocorticoid receptor a (GRa) agonist, its antagonist mifepristone (MFP), or both drugs (DþM) at noon. A group of mice was subjected to surgical adrenalectomy (AdrX). Retinas were studied by histology, immunohistochemistry, TUNEL procedure, and Western blotting at different periods after pharmacological or surgical intervention (6 hours, 48 hours, or 7 days). RESULTS. The antiapoptotic molecule Bcl-X L significantly increased 6 hours after DEX injection. By contrast, this molecule could no longer be found after MFP injection. At the same time, high levels of cleaved caspase-3 (CC-3) and Bax appeared in retinal extracts, and TUNEL þ nuclei selectively showed in the outer nuclear layer (ONL). After MFP, retinal extracts also contained phosphorylated histone H2AX (p-H2AX), a marker of DNA breakage and repair. Loss of ONL nuclear rows and decrease of rhodopsin levels were evident 7 days after MFP administration. These changes were minimized when DEX was given together with MFP (DþM). In the absence of MFP, DEX increased Bcl-X L in every retinal layer, with a marked intensification in photoreceptor inner segments. Numerous TUNEL þ nuclei rapidly appeared in the ONL after AdrX. CONCLUSIONS. A single dose of MFP induced selective photoreceptor damage in the absence of other environmental stressors. Because damage was prevented by DEX, and was reproduced by AdrX, our findings suggest that glucocorticoids play a critical role in photoreceptor survival. (Invest Ophthalmol Vis Sci. 2013;54:313-322