Neuropeptide GPCRs

The structural analysis of membrane-associated peptides comprises two steps (a) the elucidation of the three-dimensional fold of the peptide and (b) the determination of the membrane-peptide interface. We will use our results gained for the 36 amino acid residue neuropeptide Y (NPY) [83] to demonstrate the approaches that can be used. NPY regulates important pharmacological functions such as blood pressure, food intake or memory retention and hence has been subject of many investigations (for a review see Ref. [84]). It targets the so-called Y receptors that belong to the class of seven transmembrane receptors coupled to G-proteins (GPCRs). 

Figure 8. GPCRs described using radar plots. From left to right metastatin receptor (GPR54), neuropeptide Y2 receptor and metabotropic glutamate receptor (mGluRS).

R) Schistosoma GPCR (SmNPRI) AY354457 Neuropeptide Y2 receptor U42766 21.3 35.9... 

Cholecystokinin receptors are the GPCRs CCK-A and CCK-B. The C-terminal sulfated octapeptide CCK fragment (CCK8) is a major neuropeptide. CCK is involved in anorexia, cardiovascular tonus, central respiratory control, nociception, pancreatic exocrine secretion, gastric emptying, memory, vigilance and emotional states such as anxiety and panic. 

Neuropeptide S Receptor 1 (NPSR1) The GPCR Associated with Asthma... 

GPCR variant relevance to disease and drug response phenotypes may be useful in modeling systems suitable for drug development— such as targeting such systems as the orexin/hypocretin neuropeptides [37]. Such analyses are, however, complicated by the variability across different populations. 

GPCRs are the largest class of receptors mediating the effects of small nenrotransmitters, all known neuropeptides, many peptide hormones and inflammatory mediators, some lipids and even calcinm for the control of its blood concentration. 

As illustrated in Fig. 15.4-2, three main families of human GPCRs are known. The rhodopsin-like family A is the largest and the best studied from the structural and functional points of view. The other two main subfamilies are the secretin-like receptor family B, which binds several neuropeptides and other peptide hormones, and the metabotropic glutamate receptor (mGluR)-like family C. A still separate group is constituted by the receptors of the frizzled family, for which the direct coupling to heterotrimeric G-proteins is still a matter of debate [5]. 

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