Insights into GProtein Coupled Receptor Sensitization Desensitization Dynamics from 5HT2CR Mutant Mouse Models

Like many G-protein-coupled transmembrane receptors, 5-HT2CRs contain a carboxy-terminal phosphorylation domain (PDZ) recognition site that participates in regulation of receptor ligand-binding sensitivity. In mutant mice bearing functional 5-HT2CRs without this PDZ recognition site (5-HT2CRÀPDZ), as anticipated, no differences in serotonin binding kinetics, maximal agonist evoked inositol phosphate formation, or intracellular calcium dynamics were appreciated. However, 5-HT2CRs from 5-HT2CRÀPDZ +/Y mice were unable to incorporate 32P after ligand binding, and displayed attenuated responses to a second round of agonist stimulation given 2.5 min after an initial stimulation (Backstrom et al. 2000). These results provide genetic evidence that the loss of the PDZ binding site impairs G-protein-coupled receptor sensitization/desensitization processes, and clearly indicate that this process plays an important role in the molecular function of 5-HT2CRs. How this difference in receptor desensitization affects behavior remains unexplored, and is an important future avenue for further studies.

Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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