Receptor functional significance

Figure 13.24 Six subfamilies of receptor tyrosine kinases involved in cell growth and differentiation. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a "kinase insert region" in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulin-like domains is unknown.

There is abundant experimental evidence suggesting that many (if not most) GPCRs exist as homodimers and/or heterodimers [4]. The functional significance of dimers and their role in G protein activation remains to be determined for most GPCRs. Experimental evidence suggests that dimers may play roles in processing and maturation of newly synthesized receptor protein. Heterodimers may contribute to pharmacologic... 

Moreover, there exist polymorphic MOP variants. An Asn40Asp polymorphism has been found with a high abundance in the Caucasian and Asian population. This receptor variant is less expressed in the brain and carrier of this polymorphism appears to need more opioids for analgesic treatment. There are many additional MOP polymorphisms with unknown functional significance. In spite of many studies there appears to exist no significant association of polymorphisms in the MOP gene and drug addiction [5]. 

According to the NC-IUPHAR Subcommittee on Opioid Receptois it was proposed to term ORL-1 recqrtor as NOP receptor [1]. The human NOP receptor gene encodes a protein of370 amino acids. Splice valiants have been found in the human and mouse NOP recqrtor with no known functional significance. NOP receptors are widely distributed throughout the brain and in the spinal cord. They are also present in immune cells. A functional role for N/OFQ has been proposed in nociception, locomotoric activity, reward, stress, and immunomodulation. 

Similar to alcohol (Lovinger and White 1991) and volatile anesthetics (Machu and Harris 1994), trichoroethane, trichloroethylene, and toluene enhance 5-HT3 receptor function. All three inhalants significantly and reversibly potentiated, in a dose-dependent manner, 5-HT-activated currents, mediated by mouse 5-HT3 receptors expressed in Xenopus oocytes. Another feature common to these drugs is that the acute use of inhalants, as well as alcohol and volatile anesthetics, can produce nausea and vomiting (Meredith et al. 1989). It is believed that 5-HT3 receptors located in the area postrema mediate this action of alcohol and the volatile anesthetics (Aapro 1991). 

The GABAb receptors were the first G-protein-coupled receptors to be observed to form functional heterodimers (Bowery and Enna 2000) where two G-protein molecules come together to act as a dimer to enhance their combined response. A similar effect has recently also been described for dopamine and somatostatin receptors (Rocheville et al. 2000) and it is likely that this may occur with other G-protein-coupled receptors. The significance of this in terms of the pharmacology of the receptors is unclear, or indeed whether dimerisation affects mechanisms such as desensitisation. 

Familial hypercholesterolaemia is characterized by a significant elevation in plasma LDL concentration. The basic metabolic defect appears to be abnormal LDL receptor function, arising from mutations in the LDL receptor gene. Several receptor mutations have been identified and hypercholesterolaemia severity as well as the age of onset of ischaemic heart disease has recently been demonstrated to vary according to the type of LDL receptor gene defect (Moorjani et al., 1993). 

The organization of chemokine families based on the cysteine sequence has functional significance. Some human chemokines can compete for binding and activation of receptors with other intrafamily chemokines. This raised the possibility that significant structural differences in chemokine-receptor interactions... 

The Functional Significance of Dimerization Is More Unclear AMONG RHODOPSIN-LlKE RECEPTORS... 

NMDAR1 receptor Schizophrenia SNPs in coding region, but no functional significance 14... 

This section summarizes the current information about different human keratins, their functional significance, cell-type-specific distribution as well as their coexpression with myoepithelial markers and estrogen receptor alpha (ER), because these markers exhibit characteristic expression patterns in some human breast tumors. In many of these cases, a definite diagnosis can be achieved only when additional information is provided by immunohistochemistry. 

---