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      Physiological Roles of GPR10 and PrRP Signaling

      review-article

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          Abstract

          Prolactin-releasing peptide (PrRP) was first isolated from bovine hypothalamus, and was found to act as an endogenous ligand at the G-protein-coupled receptor 10 (GPR10 or hGR3). Although originally named as it can affect the secretion of prolactin from anterior pituitary cells, the potential functions for this peptide have been greatly expanded over the past decade. Anatomical, pharmacological, and physiological studies indicate that PrRP, signaling via the GPR10 receptor, may have a wide range of roles in neuroendocrinology; such as in energy homeostasis, stress responses, cardiovascular regulation, and circadian function. This review will provide the current knowledge of the PrRP and GPR10 signaling system, its putative functions, implications for therapy, and future perspectives.

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          Most cited references75

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          A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.

          The mammalian olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants presumably results from the association of odorous ligands with specific receptors on olfactory sensory neurons. To address the problem of olfactory perception at a molecular level, we have cloned and characterized 18 different members of an extremely large multigene family that encodes seven transmembrane domain proteins whose expression is restricted to the olfactory epithelium. The members of this novel gene family are likely to encode a diverse family of odorant receptors.
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            Sleep, epilepsy and thalamic reticular inhibitory neurons.

            M Steriade (2005)
            Thalamic reticular neurons release the potent inhibitory neurotransmitter GABA and their main targets are thalamocortical neurons in the dorsal thalamus. This article focuses on two topics: (i) the role of thalamic reticular neurons in the initiation of spindles, a hallmark oscillation during early sleep stages; and (ii) the reticular-induced inhibition of thalamocortical neurons during cortically generated spike-wave seizures. Although hotly debated during the past decade, the idea of spindle generation by a network of GABAergic reticular neurons was recently supported by in vivo and in computo studies demonstrating interactions between inhibitory reticular neurons that lead to spindle sequences. During spike-wave seizures and electrical paroxysms of the Lennox-Gastaut type, which arise in the neocortex, reticular neurons are powerfully excited through corticofugal projections and they produce prolonged inhibitory postsynaptic potentials in thalamocortical neurons. Thus, GABAergic reticular neurons are crucial in the generation of some sleep rhythms, which produce synaptic plasticity, and in inhibiting external signals through thalamocortical neurons, which leads to unconsciousness during absence epilepsy.
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              Evolution of Leptin Structure and Function

              Leptin, the protein product of the obese (ob or Lep) gene, is a hormone synthesized by adipocytes that signals available energy reserves to the brain, and thereby influences development, growth, metabolism and reproduction. In mammals, leptin functions as an adiposity signal: circulating leptin fluctuates in proportion to fat mass, and it acts on the hypothalamus to suppress food intake. Orthologs of mammalian Lep genes were recently isolated from several fish and two amphibian species, and here we report the identification of two Lep genes in a reptile, the lizard Anolis carolinensis . While vertebrate leptins show large divergence in their primary amino acid sequence, they form similar tertiary structures, and may have similar potencies when tested in vitro on heterologous leptin receptors (LepRs). Leptin binds to LepRs on the plasma membrane, activating several intracellular signaling pathways. Vertebrate LepRs signal via the Janus kinase (Jak) and signal transducer and activator of transcription (STAT) pathway. Three tyrosine residues located within the LepR cytoplasmic domain are phosphorylated by Jak2 and are required for activation of SH2-containing tyrosine phosphatase-2, STAT5 and STAT3 signaling. These tyrosines are conserved from fishes to mammals, demonstrating their critical role in signaling by the LepR. Leptin is anorexigenic in representatives of all vertebrate classes, suggesting that its role in energy balance is ancient and has been evolutionarily conserved. In addition to its integral role as a regulator of appetite and energy balance, leptin exerts pleiotropic actions in development, physiology and behavior.
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                Author and article information

                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                05 March 2013
                2013
                : 4
                : 20
                Affiliations
                [1] 1Faculty of Life Sciences, AV Hill Building, University of Manchester Manchester, UK
                Author notes

                Edited by: Hubert Vaudry, University of Rouen, France

                Reviewed by: Günter K. Stalla, Max-Planck-Institute of Psychiatry, Germany; Tatsushi Onaka, Jichi Medical University, Japan

                *Correspondence: Simon M. Luckman, Faculty of Life Sciences, AV Hill Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK. e-mail: simon.luckman@ 123456manchester.ac.uk

                This article was submitted to Frontiers in Neuroendocrine Science, a specialty of Frontiers in Endocrinology.

                Article
                10.3389/fendo.2013.00020
                3587801
                23467899
                e847ad9e-94f8-4988-979c-7cd26c0e30a0
                Copyright © 2013 Dodd and Luckman.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 11 January 2013
                : 19 February 2013
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 83, Pages: 9, Words: 7977
                Categories
                Endocrinology
                Review Article

                Endocrinology & Diabetes
                prrp,gpr10,energy intake,stress,dorsomedial hypothalamic nucleus,nucleus tractus solitarius,energy metabolism

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