Identifying the putative G protein coupled receptor/s candidates of cocaine and amphetamine regulated transcript (CART) peptide

Download
2014
Kasap, Merve
Cocaine and amphetamine regulated transcript (CART) peptides are neurotransmitters and endocrine factors in the nervous system and periphery. CARTPT codes for a neuropeptide hormone with a number of biological roles which are important for the mammalian physiology such as controlling feeding behavior, drug reward, bone remodeling, sensory processing, neuroendocrine function, stress anxiety, cardiovascular function, gastrointestinal motility and development. In hypothalamus, behavioral and drug studies showed that CART can suppress the feeding behavior. Also, due to having neuroprotective and survival promoting properties, and ability to initiate differentiation of neurons in vitro, CART peptides appear early in the development of the CNS and other tissues. It is suggested that they have a role in the development of specific regions of the brain, GI tract, pancreas and ovary. Although CART peptide plays very important roles and has important physiological functions, CART receptor/s has not been identified yet. There are two forms of the CART peptide: CART-I (55–102) and CART-II (61–102). These active forms cause an increase in c-Fos levels in a variety of neurons.Because of the observed effects of CART peptide on differentiation and development, CART 55–102 effects are examined to alter the MAPK cascade and the phosphorylation state of ERK1 and 2. ERKs are known to be activated by a variety of growth factors, hormones and neurotransmitters. It is found that CART peptide stimulation strongly regulates ERK activity in pituitary-derived cell lines. The CART effect is blocked by inhibitors such as U0126, genistein and pertussis toxin, indicating the involvement of the upstream kinases, MEK1 and 2. Therefore, the involvement of a Gi/G0 coupled GPCR in CART signaling is considered as possibility. Gi/G0 is a member of α subunit of heterotrimeric G-protein that inhibits the production of cAMP from ATP. Also, previous electrophysiological studies suggested that the effects of CART may involve G-proteins, but concrete biochemical evidence for a G-protein-mediated pathway activated by CART has been lacking. The CART receptor is suspected to be a GPCR, possibly one that coupled to Gi/G0.

Suggestions

Alterations of hypothalamic neuropeptides involved in food intake and appetite in olanzapine monotherapy
Sezlev, Deniz; Yanık, Tülin; Department of Biology (2012)
The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and ...
Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26
Aktas, Y; Yemisci, M; Andrieux, K; Gursoy, RN; Alonso, MJ; Fernandez-Megia, E; Novoa-Carballal, R; Quinoa, E; Riguera, R; Sargon, MF; Celik, HH; Demir, Ayhan Sıtkı; Hincal, AA; Dalkara, T; Capan, Y; Couvreur, P (American Chemical Society (ACS), 2005-11-01)
The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (...
The effects of early postnatal ethanol intoxication on retina ganglion cell morphology and the development of retino-geniculate projections in mice
Dursun, İlknur; Jakubowska Doğru, Ewa; Department of Biology (2011)
Experimental and clinical data have documented the adverse effects of perinatal ethanol intoxication on peripheral organs and the central nervous system. There is little known, however, about potential damaging effects of perinatal ethanol on the developing visual system. The purpose of this study was to examine the effects of neonatal ethanol intoxication on RGC morphology, estimate the total number of neurons in RGC layer and dorsolateral geniculate nucleus (dLGN), and on the eye-specific fiber segregatio...
Analysis of Protein and mRNA Expressions of CYP1A1 and CYP2E1 Enzymes In Liver, Colon And Prostate Cancer Cell Lines to Study Drug and Carcinogen Metabolism
Evin, Emre; Akkulak, Merve; Adalı, Orhan (null; 2017-10-29)
Most of the marketed drugs are metabolized by Cytochrome P450s (CYPs) known as phase I enzymes. A phase I enzyme, CYP1A1 catalyzes the conversion of many pro-carcinogens and hydroxylation of many endogenous substrates. CYP2E1 is also important in the metabolism of drugs, pre-toxins and pro-carcinogens. The present study was aimed to describe the best cell line model for studying phase I xenobiotic metabolizing CYP1A1 and CYP2E1 enzymes and possible effects of xenobiotics on these enzymes. In this study HT29...
Determination of hypothalamic neuropeptide levels involved in appetite regulation in atypical antipsychotic drug, risperidone treatment
Kurşungöz, Canan; Yanık, Tülin; Department of Biology (2012)
Although the use of atypical antipsychotic drugs is successful in the treatment of schizophrenia, they cause complications in the long term use that is mainly weight gain. In this study, circulating levels of hypothalamic neuropeptides/hormones, which are related to appetite regulation; neuropeptide Y (NPY), alpha melanocyte stimulating hormone (α-MSH), cocaine and amphethamine regulated transcript (CART) and plus leptin in male schizophrenic patients who were treated with an atypical antipsychotic drug, ri...
Citation Formats
M. Kasap, “Identifying the putative G protein coupled receptor/s candidates of cocaine and amphetamine regulated transcript (CART) peptide,” M.S. - Master of Science, Middle East Technical University, 2014.