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

Thesis Type: Postgraduate

Institution Of The Thesis: Orta Doğu Teknik Üniversitesi, Faculty of Arts and Sciences, Department of Biology, Turkey

Approval Date: 2014




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.