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Kappa opioid receptor (KOR) belongs to the opioid system. This system plays an essential role in addiction. Opioid receptors and endogenous opioid peptides are very widely present in brain structures that control reward phenomena, particularly the mesolimbic system. These opioid receptors and peptides participate selectively in several aspects of the addictive processes induced by opiates, cannabinoids, psychostimulants, alcohol and nicotine.
Structure
Function
The kappa opioid receptor, just as the oher opioid receptors is a powerful analgesic and hence could be used as a pain regulator. Nevertheless, unlike other opioid receptors such as morphin, the clinical use of the KOR is extreamely rare because of the impornt psychological effects triggered by this receptor such as dysphoria, dissociations or drug predispositions :
By using a forced swim stress test, it has been determined that the releasing of endogenous dynorphin opioids (which are KOR agonists) by the organism in a stress situation activates the kinase fonction of the KOR which leads to the phosphoryllation of ERK1/2 MAPK. Hence the activation of their pathways which leads to he attenuation of stress effects over the organism.
However, it appears that regular stress situations, so regular ERK1/2 MAPK activation, cause the well known psychological problems which prevent the use of the kappa opioids as pain regulators.
It has also been proved that the mice possessing inactiv KOR due to prior inhibition by KOR antagonists have proved to be inapt to activate the ERK1/2 MAPK pathways due to the non posphorylation of those two. Thus those mice didn’t show any sign of psychological disorder.
Therefore the KOR antagonist molecules are now looked for their potenial against all type of addiction.
Relevance
Structural highlights
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