Vasopressin and oxytocin expression in hypothalamic supraoptic nucleus and plasma electrolytes changes in water-deprived male Meriones libycus

International audienceABSTRACT In mammals, plasmatic osmolality needs to be stable, and it is highly related to the hydric state of the animals which depends on the activity of the hypothalamic neurohypophysial system and more particularly by vasopressin secretion. Meriones, a desert rodent, can survive even without drinking for more than one month. The mechanism(s) by which they survive under these conditions remains poorly understood. In this study, we examine the water’s deprivation consequences on the: (1) anatomy, morphology, and physiology of the hypothalamic supraoptic nucleus, (2) body mass and plasma electrolytes changes in male desert rodents ‘Meriones libycus’ subjected to water deprivation for 30 days. The effect of water deprivation was evaluated on the structural and cellular organization of the supraoptic nucleus by morphological observations and immunohistochemical approaches, allowing the labeling of AVP but also oxytocin. Our finding demonstrated that upon water deprivation (1) the body weight decreased and reached a plateau after a month of water restriction. (2) The plasmatic osmolality began to decrease and return to values similar to control animals at day 30. (3) The SON, both in hydrated and water-deprived animals, is highly developed.(4) The AVP labeling in the SON increased upon dehydration at variance with OT. These changes observed in body mass and plasma osmolality reveal an important adaptive process of male Meriones in response to prolonged water deprivation. Overall, this animal represents an interesting model for the study of water body homeostasis and the mechanisms underlying the survival of desert rodents to xeric environments

A GIPC1-palmitate switch modulates dopamine drd3 receptor trafficking and signaling

WOS: 000372330700014PubMed ID: 26787837Palmitoylation is involved in several neuropsychiatric and movement disorders for which a dysfunctional signaling of the dopamine D3 receptor (Drd3) is hypothesized. Computational modeling of Drd3's homologue, Drd2, has shed some light on the putative role of palmitoylation as a reversible switch for dopaminergic receptor signaling. Drd3 is presumed to be palmitoylated, based on sequence homology with Drd2, but the functional attributes afforded by Drd3 palmitoylation have not been studied. Since these receptors are major targets of antipsychotic and anti-Parkinsonian drugs, a better characterization of Drd3 signaling and posttranslational modifications, like palmitoylation, may improve the prospects for drug development. Using molecular dynamics simulations, we evaluated in silico how Drd3 palmitoylation could elicit significant remodeling of the C-terminal cytoplasmic domain to expose docking sites for signaling proteins. We tested this model in cellulo by using the interaction of Drd3 with the G-alpha interacting protein (GAIP) C terminus 1 (GIPC1) as a template. From a series of biochemical studies, live imaging, and analyses of mutant proteins, we propose that Drd3 palmitoylation acts as a molecular switch for Drd3-biased signaling via a GIPC1-dependent route, which is likely to affect the mode of action of antipsychotic drugs.Fondation pour la recherche medicale; French ministry of research; Fondation de FranceFondation pour la recherche medicale provided funding to Pierre Sokoloff and Freddy Jeanneteau. French ministry of research provided funding to Freddy Jeanneteau. Fondation de France provided funding to Margarita Arango-Lievano and Freddy Jeanneteau

Acute and chronic hyperglycemic effects of vasopressin in normal rats : Involvement of V1A receptors

Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1A and V1B receptors (R) are expressed in the liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague-Dawley rats, as well as the respective roles of V1AR and V1BR. We showed that acute injection of AVP induces a dosedependent increase in glycemia. Pretreatment with a selective V1AR antagonist, but not a V1BR antagonist, dose-dependently prevented the rise in glycemia. V1BR antagonism did not modify the hyperinsulinemic response, resulting from AVP-induced hyperglycemia, but enhanced the fall in glucagonemia. Acute administration of selective V1AR or V1BR agonists confirmed the involvement of V1AR in the hyperglycemic effect of AVP. In chronic experiments, AVP levels were altered in both directions. Sustained AVP infusion through implantable minipumps induced a time-dependent increase in fasting glycemia, whereas lowering endogenous AVP by increasing water intake had no effect. After 4 wk of AVP infusion, the rise in glycemia amounted to 1.1 mmol/l (P < 0.01) without significant change in insulinemia. This effect was attenuated by cotreatment with a V1AR antagonist. Similar results were observed in lean Zucker rats. These findings demonstrate for the first time a causal link between chronic high AVP and hyperglycemia through V1AR activation and, thus, provide a pathophysiological explanation for the relationship observed in human cohorts between the AVP-hydration axis and the risk of diabetes

Structure and function of G protein coupled receptors

The G protein coupled receptors (GPC-Rs) comprise a large superfamily of genes encoding numerous receptors which all show common structural features, e.g., seven putative membrane spanning domains. Their biological functions are extremely diverse, ranging from vision and olfaction to neuronal and endocrine signaling. The GPC-Rs couple via multiple G proteins to a growing number of recognized second messenger pathway, e.g., cAMP and phosphatidyl inositol turnover. This review summarizes our current knowledge of the molecular mechanisms by which the GPC-Rs activate second messenger systems, and it addresses their regulation and structure