Opioid receptors splice variants

Pan YX, Xu J, Mahurter L, et al Identification and characterization of two new human mu opioid receptor splice variants, hMOR-lO and hMOR-lX. Biochem Biophys Res Commun 301 1057-1061, 2003... 

There is also high sequence homology with opioid receptors in the intracellular loops, consistent with ORLl receptors coupling to the same G-proteins as opioid receptors. Splice variants of the ORLl gene have been reported (see Refs. 87,90 for reviews),and the results of some pharmacological studies have suggested receptor heterogeneity (see Ref 87), but the existence of subtypes of the ORLl receptor has not been firmly established. 

Opioids act on heptahelical G-protein-coupled receptors. Three types of opioid receptors (p, 8, k) have been cloned. Additional subtypes (e.g., pl3 p2, 81 82), possibly resulting from gene polymorphisms, splice variants or alternative processing have been proposed. Opioid receptors are localized and can be activated... 

In addition to in vitro cell models, opioid agonists could induce the rapid endocytosis of the receptor in organo cultures or primary neuronal cultures, and also neurons in vivo. Treatment of longitudinal muscle-myenteric plexus preparation or the primary hippocampal neuron cultures with DAMGO resulted in internalization of the mu opioid receptor [146,147]. Similar observation was obtained with fluorescently labeled opioid peptides Fluo-dermorphin and Fluo-deltorphin [148]. Within 15 min of an intra-peritoneal injection of etorphine, mu opioid receptor immunoreactivity was observed in the endosomal structures of the myenteric neurons of guinea pig ileum [149]. Again, rapid clustering of a spliced variant of mu opioid receptor MOR-1C was observed in the lateral septum of the mouse after intracere-... 

However, it is clear that opioid receptor endocytosis is critical for the receptor to resensitize. Wolf et al. [170] reported the mutation of Thr394 of mu opioid receptor to Ala resulted in the rapid internalization and resensitization of receptor. Similar observations were reported with various spliced variants of mu opioid receptor, in which the rate of desensitization appears to correlate inversely with the resensitization properties of receptor [169]. Such observations and others have led to a hypothesis proposed by Whistler et al. [140] that the ability of various opioid agonists to produce tolerance is dependent on their RAVE values. In their hypothesis, agonist that induces rapid receptor internalization, e.g., etorphine, would develop less tolerance in animals than agonist such as morphine, which does not produce receptor... 

Receptor Subtypes, Splice Variants, and Receptor Dimerization, Before cloning of the opioid receptors, subtypes of each of the three opioid receptors were proposed on the basis of evidence from pharmacological assays (see Refs. 69, 103 for excellent reviews), although opioid receptors identified by cloning have consistently represented only a single subtype for each receptor type. Currently, there is still considerable debate on the existence and nature of some of these receptor subtypes. 

Pan YX, Xu J, Bolan E, Moskowitz HS Pasternak GW. Identification of four novel exon 5 splice variants of the mouse mu opioid receptor gene. Mol Pharmacol Fast Forward 2005 68 866-875. 

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