Neuropeptide receptor

Fig. 5. Schematic diagram of the presumed arrangement of the amino acid sequence for the 5-opioid receptor, showing seven putative transmembrane segments three intracellular loops, A three extracellular loops, B the extracellular N-terrninus and the intracellular C-terrninus, where (0) represents amino acid residues common to ] -, 5-, and K-receptors ( ), amino acid residues common to all three opioid receptors and other neuropeptide receptors and (O), other amino acids. Branches on the N-terruinal region indicate possible glycosylation sites, whereas P symbols in the C-terminal region indicate...

Amino acid receptors Monoamine receptors Lipid receptors Purine receptors Neuropeptide receptors Peptide hormone receptors Chemokine receptors Glycoprotein receptors Protease receptors Metabotropic glutamate and GABAb receptors Adrenoceptors, dopamine and 5-HT receptors, muscarinic and histamine receptors Prostaglandin, thromboxane and PAF receptors Adenosine and ATP (P2Y) receptors Neuropeptide Y, opiate, cholecystokinin VIP, etc. Angiotensin, bradykinin, glucagon, calcitonin, parathyroid, etc. Interleukin-8 TSH, LH/FSH, chorionic gonadotropin, etc. Thrombin... 

Most neuropeptide receptors are seven-transmembrane-domain, G-protein-coupled receptors 326 Neuropeptide receptors are not confined to synaptic regions 327 Expressions of peptide receptors and the corresponding peptides are not well matched 327... 

The amiloride-sensitive FMRF-amide-gated sodium ion channel is among the few peptide-gated ion channels identified 328 Neuropeptide receptors are becoming molecular targets for therapeutic drugs 328... 

Neuropeptide receptors are not confined to synaptic regions. Peptidergic neurotransmission often operates on a slower time scale than conventional neurotransmitters, so it is not surprising that peptide receptors are often localized at a distance from the synapse. For example, although some substance P terminals contact membranes loaded with substance P receptor, only a small fraction of the substance P receptor-laden membrane is apposed to synaptic terminals. Substance P may diffuse a considerable distance from its release site and still find a receptor with which it can interact [21]. 

Neuropeptides play key roles in appetite regulation and obesity. Many genes for neuropeptides and neuropeptide receptors have been implicated in obesity and cachexia, anorexia and bulimia [34]. For example,NPY administration into the CNS causes overeating and obesity. A second peptide involved in obesity is leptin, a product of adipocytes and the stomach. The leptin gene is defective in the ob/ob mouse but in normal mice leptin binds to its receptor in the hypothalamus, causing a decrease in the synthesis and release of hypothalamic NPY. 

One of the best-characterized effectors and second messenger systems is the cAMP cascade that can be either activated or inhibited by neurotransmit-ter/neuropeptide receptors, including those implicated in anxiety/stress such as CRE Receptors that activate cAMP synthesis couple with the stimulatory G protein, Gsa, and those that inhibit this second messenger couple with the inhibitory G protein, Gia, and these either stimulate or inhibit adenylyl cyclase, the effector enzyme responsible for synthesis of cAMP (Duman and Nestler 1999). There are at least nine different forms of adenylyl cyclase that have been identified by molecular cloning, each with a unique distribution in the brain. The different types of adenylyl cyclase are activated by Gsa as well as the diterpene forskolin, but are differentially regulated by Gia, the Py subunits, Ca, and by phosphorylation. This provides for fine control of adenylyl cyclase enzyme activity and regulation by other effector pathways. 

Fritschy JM, Johnson DK, Mohler H, Rudolph U (1998) Independent assembly and subcel-lular targeting of GABAA receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. Neurosci Lett 249 99-102 Griebel G (1999) is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders. Pharmacol Ther 82 1-61... 

A gastrinlike neuropeptide, CCK exists in the central nervous system both as an octapeptide [CCK-8] and as a tetrapeptide (CCK-4) (Rex et al. 1994b). The octapeptide CCK-8 occurs predominantly in sulfated form and is one of the most abundant neuropeptides in the central nervous system (Rex et al. 1994b]. Two major subtypes of CCK receptors, labeled as CCK-A and CCK-B receptors, have been identified (Hill et al. 1993]. At this point, the most promising neuropeptide receptor to target for the treatment of anxiety may be the CCK-B receptor. This receptor is widely distributed throughout... 

Parker SL, Balasubramaniam A Neuropeptide Y Y2 receptor in health and disease. Br J Pharmacol 2008 153 420. [PMID 17828288] Schlicker E, Kathmann M Presynaptic neuropeptide receptors. Handb Exp Pharmacol 2008(184) 409. 

Betancur, C., Azzi, M., Rostene, W. Nonpeptide antagonists of neuropeptide receptors tools for research and therapy, Trends Pharmacol. Sci. 1997, 18, 372-383. 

Neuropeptides are degraded by enzymes called neutral endopeptidases, which are present adjacent to neuropeptide receptors. Neutral endopeptidases regulate the neuropeptide-induced responses by modulating their levels. Inhibitors of these enzymes are being studied as a potential therapeutic agent for asthmatic disease. In... 

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