Mutant 8 opioid receptor

Huang, P., Visiers, I., Weinstein, H., and Fiu-Chen, F.-Y. (2002) The local environment at the cytoplasmic end of TM6 of the m opioid receptor dilfers from those of rhodopsin and monoamine receptors introduction of an ionic lock between the cytoplasmic ends of helices 3 and 6 by a L6.30(275)E mutation inactivates the m opioid receptor and reduces the constitutive activity of its Thr6.34(279)K mutant. Biochemistry 41, 11972-11980. 

The activation of Erkl/2 by opioid receptor has been shown to occur through the G(5y subunits in a Ras-dependent manner [101]. However, whether the delta opioid receptor activation of the Erkl/2 requires the receptor being internalized is controversial. Coscia and coworkers suggested that delta opioid receptor internalization is a prerequisite for the agonist activation of the Erkl/2 [102]. However, several laboratories have since reported that opioid receptor activation of Erkl/2 did not depend on the receptor internalization [103,104]. Dominant negative dynamin mutant that would block the agonist-induced receptor internalization would not attenuate the Erkl/2 stimulation. Such data support the observation that morphine could stimulate the Erkl/2 activity but could not induce receptor internalization [105], Thus, the delta opioid receptor stimulates the Erkl/2 activities prior to the receptor internalization processes. 

In addition to the G(Vy subunit mechanism, the opioid receptor could increase the Erkl/2 activity via a transactivation process. Using receptor mutants that have impeded calmodulin binding activity, Belvecha et al. [106] demonstrated the activation of Erkl/2 by the mu opioid receptor involved the calmodulin-dependent transactivation of the EGF receptor. Such mechanism represents the participation of metalloproteases in producing the ligand for EGF receptor as in the case of p>2-adrcncrgic receptor [107]. Whether this is occurring with the neuronal delta opioid receptor remains to be demonstrated. 

In HEK cells coexpressing the delta opioid receptor and a constitutively active mutant of Gas and adenylyl cyclase type II, delta agonists cause Gfky-mediated stimulation of adenylyl cyclase type II [55]. Agonist action at delta receptors expressed in COS-7 cells or HEK 293 cells has been shown to stimulate the MAP kinase pathway, possibly mediated by Gfky subunits [56,57],... 

Connor M, SchuUer A, Pintar JE, Christie MJ (1999) Mu-opioid receptor modulation of calcium channel current in periaqueducal grey neurons from C57B16/J mice and mutant mice lacking MOR-1. BrJ Pharmacol 126 1553-1558... 

Tryoen-Toth P, Decaillot FM, Filliol D, Befort K, Lazarus LH, Schiller PW, Schmidhammer H, Kieffer BL (2005) Inverse agonism and neutral antagonism at wild type and constitutively active mutant 5 opioid receptors. J Pharmacol Exp Ther 313 410-421... 

Jones RM, Hjorth SA, Schwartz TW, Portoghese PS (1998) Mutational evidence for a common k antagonist binding pocket in the wild-type k and mutant p[K303E] opioid receptors. J Med Chem 41 4911-4914... 

INTERACTION OF UGANDS WITH CLONED WILD-TYPE AND MUTANT DELTA OPIOID RECEPTORS... 

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