B Receptors

Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

BK actions are mediated through at least two types of GPCR B and B2. At the B receptor, des-Arg BK is more potent than BK. The converse is tme at the B2 receptor. The effects of BK are primarily mediated by activation of the B2 receptor because the B receptor has limited tissue distribution and is iaduced by noxious stimuli such as apamin or an inflammatory mediator-type response. The existence of a B receptor was suggested on the basis of limited efficacy of known antagonists ia some systems. A B receptor may also exist. The human B2 receptor has been cloned. 

Figure 6.9. Geometry of a radiative sphere (fireball). (A) receptor sees the whole fireball. (B) receptor sees part of the fireball.

III. Tyr protein kinases A. Cytosolic tyrosine kinases src, fgr, abl, etc.) B. Receptor tyrosine kinases (RTKs) Plasma membrane receptors for hormones such as epidermal growth factor (EGF) or platelet-derived growth factor (PDGE) Raf (a protein kinase)... 

Figure 46.3 Types of hoods, (a) Enclosure (b) receptor (c) captor...

Khodorova A, Navarro B, Jouaville LS et al (2003) Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med 9 1055-1061... 

Smad anchor for receptor activation) An intracellular protein Sara which accumulates at early endosomes and plays a key role in TGF- 3 signal transduction through the recruitment of receptor activated R-Smads for phosphorylation by the type ITGF-B receptor. 

Tachykinin NK3 receptor TK NK3r Neurokinin-3 receptor, neurokinin B receptor, neurokinin-beta receptor, Neuromedin K receptor... 

Bowery, NG and Enna, SJ (2000) Gamma-aminobut5Tic acid(B) receptors first of the functional metabotropic heterodimers. J. Pharmacol. Exp. Ther. 292(1) 2-7. 

K, Alder, F, Smith, A, McKernan, R, Metters, K, O Neill, GP, Facaille, JC and Hebert TE (2001) y-Aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol. Pharmacol. 59 144-152. 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

Finally, the peptide can induce anxiety and panic in normal and anxious volunteers. Some synthetic CCK-B receptor antagonists are chemically similar to the benzodiazepine anxiolytics. Again, the clinical role of CCK manipulation in anxiety remains to be resolved. 

FIG. 19 Normalized concentration profiles (solid lines) of the reactants and products in the DCE (a) or aqueous (b) receptor phase for the reaction between Fc (DCE) and IrClg (aqueous) with 0.1 M CIO4 in both DCE and the aqueous phase. In each case, the reactant concentration in the receptor phase was 1 mM, with 10 mM reactant inside the droplet. Drop times and final sizes were (a) 5.54 s and 0.96 mm, and (b) 6.32 s and 1.00 mm. The theoretical profiles (dashed lines) are for a transport-controlled reaction, with no transfer of the product ions. (Reprinted from Ref. 80. Copyright 1999, Royal Society of Chemistry.)... 

Endothelin-1, one of the most potent physiologic vasoconstrictors, is an important contributor to HF pathophysiology.9 Endothelin-1 binds to two G-protein coupled receptors, endothelin-A (ET-A) and endothelin-B (ET-B). Endothelin-A receptors mediate vasoconstriction and are prevalent in vascular smooth muscle and cardiac cells. Endothelin-B receptors are expressed on the endothelium and in vascular smooth muscle, and receptor stimulation mediates vasodilation. Levels of ET-1 correlate with HF functional class and mortality. 

Kaupmann K, Malitschek B, Schuler V, et al. GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 1998 396(6712) 683—687. 

The endothelin B receptor is an example of characterization of a homogeneous, affinity purified protein (Roos et al., 1998). Significant progress has been made in the development of techniques for more high-throughput identification of phosphorlyation events. Analysis of large sets of phosphorylated proteins is facilitated by the availability of affinity purification methods such as anti-phosphotyrosine or anti-phosphoserine antibodies or metal affinity chromatography (Neubauer and Mann, 1999 Soskic et al., 1999). These methods are not specific to a particular protein but rather are used to fractionate all proteins that are phosphorylated. 

Soskic, V., Gorlach, M., Poznanovic, S., Boehmer, F. D., and Godovac-Zimmermann, J. (1999). Functional proteomics analysis of signal transduction pathways of the platelet-derived growth factor b receptor. Biochemistry 38, 1757-1764. 

The Pharmacological Phenotype of Certain Family B Receptors Is Determined... 

Members of a Subfamily of Family B Receptors Are Structurally Similar... 

GABA(B) receptor antagonist on the sleep-waking cycle in the rat. Brain Res. 773, 8-14. 

Initially, it was proposed that the 5-HTjb receptor is located exclusively in the brain of the rat and some other rodents, whereas the 5-HTid receptor, a close species homolog, is specific to the guinea pig and higher mammalian species, including humans (Waeber et al., 1989). However, recent studies have characterized the 5-HTiB receptor also in the human brain (Bidmon et al., 2001 Varnas et al., 2005). The 5-HT, B receptor is linked to the inhibition of adenylate cyclase, and is located at presynaptic (5-HT axon terminals) and postsynaptic... 

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