Home About us Contact
|
Home About us Contact | ||
|
|
||
Receptor Targets (receptor + target)
Selected AbstractsDevelopmental shift in bidirectional functions of taurine-sensitive chloride channels during cortical circuit formation in postnatal mouse brainDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2004Mika Yoshida Abstract Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in the developing mammalian cerebral cortex, however, few studies have reported its neurobiological functions during development. In this study, by means of whole-cell patch-clamp recordings, we examined the effects of taurine on chloride channel receptors in neocortical neurons from early to late postnatal stages, which cover a critical period in cortical circuit formation. We show here that taurine activates chloride channels in cortical neurons throughout the postnatal stages examined (from postnatal day 2 to day 36). The physiological effects of taurine changed from excitatory to inhibitory due to variations in the intracellular Cl, concentration during development. An antagonist blocking analysis also demonstrated a developmental shift in the receptor target of taurine, from glycine receptors to GABAA receptors. Taken together, these results may reflect genetically programmed, bidirectional functions of taurine. At the early developmental stage, taurine acting on glycine receptors would serve to promote cortical circuit formation. As cortical circuit has to be regulated in the later stages, taurine would serve as a safeguard against hyperexcitable circuit. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 166,175, 2004 [source] GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesityBRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2008H A Overton GPR119 is a G protein-coupled receptor expressed predominantly in the pancreas (,-cells) and gastrointestinal tract (enteroendocrine cells) in humans. De-orphanization of GPR119 has revealed two classes of possible endogenous ligands, viz., phospholipids and fatty acid amides. Of these, oleoylethanolamide (OEA) is one of the most active ligands tested so far. This fatty acid ethanolamide is of particular interest because of its known effects of reducing food intake and body weight gain when administered to rodents. Agonists at the GPR119 receptor cause an increase in intracellular cAMP levels via G,s coupling to adenylate cyclase. In vitro studies have indicated a role for GPR119 in the modulation of insulin release by pancreatic ,-cells and of GLP-1 secretion by gut enteroendocrine cells. The effects of GPR119 agonists in animal models of diabetes and obesity are reviewed, and the potential value of such compounds in future therapies for these conditions is discussed. British Journal of Pharmacology (2008) 153, S76,S81; doi:10.1038/sj.bjp.0707529; published online 26 November 2007 [source] Which comes first: atypical antipsychotic treatment or cardiometabolic risk?ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009S. M. Stahl Objective:, To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment. Method:, A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. Results:, Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics. Conclusion:, Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic-related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death. [source] Review article: new receptor targets for medical therapy in irritable bowel syndromeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. CAMILLERI Summary Background, Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities. Aims, To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT4 agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics. Methods, Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy. Results, The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT4 agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents ,borrowed' from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study. Conclusions, There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal. [source] Mediators and receptors in the resolution of inflammation: drug targeting opportunitiesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2009AG Stewart The active resolution of inflammation is recognized as offering new opportunities to generate novel anti-inflammatory agents. The emerging appreciation of the importance of active resolution in regulation of inflammation also creates an imperative to examine developing and existing agents for their potential to influence these pathways. This themed issue of the British Journal of Pharmacology contains papers that discuss the roles of annexin-1, lipoxins and related lipid products of fish oils as well as other mechanisms involved in active resolution and their receptor targets. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 [source] GABAC RECEPTOR ION CHANNELSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2004M Chebib SUMMARY 1.,The present review gives an overview of studies conducted on GABAC receptors over the past 10 years since the author started at the University of Sydney. It concentrates on the structure,activity relationship profiles of the receptor and how these studies were used to: (i) develop selective GABAC receptor ligands; and (ii) understand the impact of amino acid changes on GABAC receptor pharmacology and function. 2.,Structure,activity relationship studies involving variations of both ligands and their receptor targets are vital to the discovery of drugs that interact selectively with particular native and mutant receptor subtypes. Such agents may be useful for treating anxiety, depression, epilepsyand memory related disorders, such as Alzheimer's disease. [source] | ||||||||||