1.Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells.
Egerod KL1, Engelstoft MS1, Lund ML1, Grunddal KV1, Zhao M1, Barir-Jensen D1, Nygaard EB1, Petersen N1, Holst JJ1, Schwartz TW1. Endocrinology. 2015 Nov;156(11):3909-23. doi: 10.1210/EN.2015-1388. Epub 2015 Jul 16.
In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we have characterized the G protein-coupled receptors expressed in gastric Sst-RFP-positive cells and probed their effects on SST secretion in primary cell cultures. Surprisingly, besides SST, amylin and PYY were also highly enriched in the SST cells. Several receptors found to regulate SST secretion were highly expressed and/or enriched. 1) The metabolite receptors calcium-sensing receptor and free fatty acid receptor 4 (GPR120) functioned as positive and negative regulators, respectively. 2) Among the neurotransmitter receptors, adrenergic receptors α1a, α2a, α2b, and β1 were all highly expressed, with norepinephrine and isoproterenol acting as positive regulators.
2.Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue.
Hirako S1, Wada N2, Kageyama H3, Takenoya F4, Izumida Y2, Kim H5, Iizuka Y5, Matsumoto A5, Okabe M6, Kimura A7, Suzuki M8, Yamanaka S8, Shioda S7. Sci Rep. 2016 Feb 19;6:21481. doi: 10.1038/srep21481.
Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals, and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP-treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid β-oxidation in liver and lipolysis in adipose tissue, and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system.
3.Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation.
Wagner L1, Kaestner F2, Wolf R3, Stiller H4, Heiser U5, Manhart S5, Hoffmann T6, Rahfeld JU7, Demuth HU7, Rothermundt M8, von Hörsten S9. Neuropeptides. 2016 Feb 27. pii: S0143-4179(16)30010-5. doi: 10.1016/j.npep.2016.02.007. [Epub ahead of print]
BACKGROUND: Dipeptidyl peptidase 4 (DPP4; EC 220.127.116.11; CD26) is a membrane-bound or shedded serine protease that hydrolyzes dipeptides from the N-terminus of peptides with either proline or alanine at the penultimate position. Substrates of DPP4 include several stress-related neuropeptides implicated in anxiety, depression and schizophrenia. A decline of DPP4-like activity has been reported in sera from depressed patient, but not fully characterized regarding DPP4-like enzymes, therapeutic interventions and protein.
4.Coexpression of Galanin and Nestin in the Chemoreceptor Cells of the Human Carotid Body.
Mazzatenta A1, Marconi GD2, Macchi V3, Porzionato A3, Cataldi A2, Di Giulio C4, Pokorski M5. Adv Exp Med Biol. 2016;885:77-82. doi: 10.1007/5584_2015_189.
The carotid body is a highly specialized chemoreceptive organ of neural crest origin whose role is to detect changes in arterial oxygen content. The sensory units are the chemoreceptor cells, which are neuronal-like cells, surrounded by sustentacular or glial-like cells. It is suggested that the carotid body contains self-renewing multipotent stem cells, which are putatively represented by glial-like sustentacular cells. The mechanisms of renewal of neuronal-like cells are unclear. Recently, we have demonstrated the expression of galanin, a peptide promoting neurogenesis, in chemoreceptor cells in the human CB. Thus, in the present study we seek to determine whether galanin expression in chemoreceptor cells could be matched with that of nestin, a peptide that is a marker of multipotent neural stem cells, or rather with the glial fibrillary acidic protein (GFAP), a marker for glial cells. The latter would underscore the pluasibly essential role of sustentacular cells in the self-renewal capability of chemorecetors.