This is the first in a series of reviews written by committees of experts of the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR). A listing of all articles in the series and the Nomenclature Reports from IUPHAR published in Pharmacological Reviews can be found at http://www. GuideToPharmacology.org. This website, created in a collaboration between the British Pharmacological Society (BPS) and the International Union of Basic and Clinical Pharmacology (IUPHAR), is intended to become a "one-stop shop" source of quantitative information on drug targets and the prescription medicines and experimental drugs that act on them. We hope that the Guide to Pharmacology will be useful for researchers and students in pharmacology and drug discovery and provide the general public with accurate information on the basic science underlying drug action.Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs -PAC1, VPAC1 and VPAC2 -belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC1 receptors are selective for PACAP, whereas VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC2 receptor in susceptibility to schizophrenia and the PAC1 receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2012 How to cite: Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR et al. (2012). control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67). LINKED ARTICLESThis article is part of a themed section o...

The receptor activity-modifying proteins (RAMPs) comprise a family of three accessory proteins that heterodimerize with the calcitonin receptor-like receptor (CL receptor) or with the calcitonin receptor (CTR) to generate different receptor phenotypes. However, RAMPs are more widely distributed across cell and tissue types than the CTR and CL receptor, suggesting additional roles for RAMPs in cellular processes. We have investigated the potential for RAMP interaction with a number of Class II G protein-coupled receptors (GPCRs) in addition to the CL receptor and the CTR. Using immunofluorescence confocal microscopy, we demonstrate, for the first time, that RAMPs interact with at least four additional receptors, the VPAC1 vasoactive intestinal polypeptide/pituitary adenylate cyclaseactivating peptide receptor with all three RAMPs; the glucagon and PTH1 parathyroid hormone receptors with RAMP2; and the PTH2 receptor with RAMP3. Unlike the interaction of RAMPs with the CL receptor or the CTR, VPAC1R-RAMP complexes do not show altered phenotypic behavior compared with the VPAC1R alone, as determined using radioligand binding in COS-7 cells. However, the VPAC1R-RAMP2 heterodimer displays a significant enhancement of agonist-mediated phosphoinositide hydrolysis with no change in cAMP stimulation compared with the VPAC1R alone. Our findings identify a new functional consequence of RAMPreceptor interaction, suggesting that RAMPs play a more general role in modulating cell signaling through other GPCRs than is currently appreciated.The discovery of receptor activity-modifying proteins (RAMPs) 1 has led to a re-evaluation of what defines G proteincoupled receptor (GPCR) phenotypic behavior toward agonists and/or G proteins (1). The RAMP family comprises three accessory proteins (designated RAMP1, RAMP2, and RAMP3) that were originally identified during attempts to clone the receptor for calcitonin gene-related peptide (CGRP). Phenotypic receptor behavior corresponding to that of the native CGRP receptor could be demonstrated only in recombinant expression systems when another seven-transmembrane receptor, the calcitonin receptor-like receptor (CL receptor) was co-expressed with RAMP1 (1). Additional studies extended these observations to identify a general role of RAMPs in modifying the expression and the pharmacology of receptors related to the calcitonin family of peptides (1-5).To date, studies of RAMP-GPCR interactions have focused predominantly on the receptors for calcitonin and its related peptides (i.e. CGRP, adrenomedullin, and amylin). However, these receptors belong to the Class II family of GPCRs, members of which share a number of structural features and are all activated by peptide ligands (6). Given these similarities, it is possible that other Class II GPCRs may also interact with RAMP proteins to yield novel receptor phenotypes or receptors with altered pharmacological profiles. Importantly, RAMPs display a ubiquitous tissue distribution (1,7,8), and cellular background can have a significant impact on ...

BackgroundUlcerative Colitis (UC) and Crohn's Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes.Methodology/FindingsExpression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05–0.19 -fold for over- and under- expression, respectively; 0.001