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Morgane Roulot,1,† Alessandra Minelli,2 Marco Bortolomasi,3 Elisabetta Maffioletti,2,4 Massimo Gennarelli,2,4 Marc Borsotto,1 Catherine Heurteaux,1 Jean Mazella1 1Molecular and Cellular Institute of Pharmacology, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d’Azur, Valbonne, France; 2Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy; 3Psychiatric Hospital “Villa Santa Chiara”, Verona, Italy; 4Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy †Morgane Roulot passed away on January 10, 2018 Purpose: Sortilin-derived propeptide (PE) and its synthetic analog spadin show strong antidepressant activity in rodents and, therefore, could be used as a biomarker to evaluate the clinical efficacy of antidepressant treatments. The aim of this study was to determine whether electroconvulsive therapy (ECT) modulates serum PE concentration in patients with treatment-resistant depression (TRD).Patients and methods: Forty-five patients with major depressive disorder, who met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were selected for this study.Results: We did not observe any difference in the PE levels between TRD patients and controls (z=0.10, P=0.92), but we found a strong significant increase between the PE levels measured just before (T0) and about 1 month (T2) after ECT (z=-2.82, P=0.005). A significant difference between T0 and T2 was observed only in responders (z=-2.59, P=0.01), whereas no effect was found in nonresponders (z=-1.27, P=0.20). Interestingly, we found a significant correlation between the increase in PE levels and decrease in Montgomery -Åsberg Depression Rating Scale scores for the total patient sample (P=0.03).Conclusion: This study indicates for the first time that ECT affects serum PE concentration in responders and, therefore, could contribute to the evaluation of the therapy success. Keywords: sortilin propeptide, electroconvulsive therapy, treatment-resistant depressed patients, diagnosis

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

Depression is a disease that is particularly frequent, affecting up to 20% of the population in Western countries. The origins of this pathology involve multiple genes as well as environmental and developmental factors leading to a disorder that remains difficult to treat. Several therapies for depression have been developed and these mainly target monoamine neurotransmitters. However, these treatments are not only associated with numerous adverse effects, but they are also ineffective for more than one-third of patients. Therefore, the need to develop new concepts to treat depression is crucial. Recently, studies using knockout mouse models have provided evidence for a crucial role of two members of the two-pore domain potassium channel ( K2P) family, tandem P-domain weak inward rectifying K+ ( TWIK)-related K+ channel 1 ( TREK-1) and TWIK-related acid-sensitive K+ channel 3 ( TASK-3) in the pathophysiology of depression. It is believed that TREK-1 and TASK-3 antagonists could lead to the development of new antidepressants. Herein, we describe the discovery of spadin, a natural peptide released from the maturation of the neurotensin receptor-3 (also known as sortilin), which specifically blocks the activity of the TREK-1 channel and displays particular antidepressant properties, with a rapid onset of action and the absence of adverse effects. The development of such molecules may open a new era in the field of psychiatry. [ABSTRACT FROM AUTHOR]

Decidual cells arise by proliferation and differentiation of endometrial stromal cells of the uterus after appropriate stimulation by ovarian hormones. Previously we have shown that progestin and relaxin stimulate the secretion of several decidual-cell-specific secretory proteins in a long-term primary cell culture system. We now report the effects of progestin and relaxin on the morphology of stromal cells in association with the production rate of two major decidual secretory proteins, prolaction and insulin-like growth factor binding protein-1 (IGFBP-1). Stromal cells were cultured in RPMI 1640 and 2% fetal bovine serum for 22 days under control conditions (no hormone), with relaxin or medroxyprogesterone acetate (MPA), or MPA plus relaxin. Cells treated with MPA alone or MPA plus porcine relaxin grew to a high density with many areas of heaping while control cells and cells grown in medium containing relaxin alone formed discontinuous layers. The cytoplasm was distinguished by aggregates of rough endoplasmic reticulum and secretory granules. Surfaces of cells treated with MPA plus relaxin had clusters of short blunt processes containing secretory granules. The processes were rarely seen in cells exposed to MPA alone and completely absent in control cells or cells exposed to relaxin alone. Intercellular space was greatly widened in cells treated with MPA alone or MPA plus relaxin. There were many extended gap junctions in MPA and relaxin-treated cells in contrast to controls. The production rates of prolactin and IGFBP-1 measured by radioimmunoassay and enzyme-linked immunosorbent assay respectively increased from 0.004 to ∼0.7 μg for prolactin and 0.01 to 44 μg for IGFBP-1 per 10 cells/day after 20 days incubation with MPA and relaxin, in agreement with the previous findings. The parallel biochemical events and morphological changes are similar to those of decidualization of endometrium from the secretory phase to the early gestation . [ABSTRACT FROM PUBLISHER]