Disease relevance of MOR

• Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat [1].
• Comparison of mu opioid receptor binding on intact neuroblastoma cells with guinea pig brain and neuroblastoma cell membranes [2].
• We hypothesize that this morphine-induced decrease in DAMGO activation of the mu-opioid receptor may be a partial explanation for the hyperventilation observed during neonatal morphine withdrawal [3].

High impact information on MOR

• Purification of the mu-opioid receptor from bovine striatum reveals a glycoprotein of Mr 65,000 which demonstrates opioid binding activity [4].
• Low concentrations of trimebutine inhibit norepinephrine release via the mu-opioid receptor and enhance intestinal motility by preventing the adrenergic inhibition of acetylcholine release [5].
• Therefore, peptide E loses mu-opioid receptor affinity (1.8-497 nmol/L) after proteolytic processing and the loss of the amino terminal tyrosine but maintains a high delta-opioid affinity (38.8-50.6 nmol/L) [6].
• Interestingly, morphine, a high-affinity MOR agonist, did not cause detectable internalization, but it partially inhibited the etorphine-induced MOR endocytosis [7].
• Abundant MOR immunoreactivity (MOR-IR) was localized to the cell body, dendrites, and axonal processes of myenteric neurons [7].

Biological context of MOR

• Porcine MOR is 96% identical with human MOR in amino acid sequence [8].
• These results demonstrate the occurrence of agonist-selective MOR endocytosis in neurons naturally expressing this receptor in vivo and suggest the existence of different mechanisms regulating cellular responsiveness to ligands [7].
• Antibody specificity was confirmed by the positive staining of human embryonic kidney 293 cells transfected with epitope-tagged MOR cDNA, by the lack of staining of cells transfected with the delta or kappa receptor cDNA, and by the abolition of staining when the MOR antibody was preadsorbed with the MOR peptide fragment [7].
• A synthetic peptide combinatorial library made up of 52,128,400 hexapeptides, each having an acetyl group at the N terminus and an amide group on the C terminus, was screened to find compounds able to displace tritiated [D-Ala2,MePhe4,Gly-ol5]enkephalin from mu opioid receptor binding sites in crude rat brain homogenates [9].
• Cyclization between D-Asp(2) and Lys(6) in c[D-Asp(2),Lys(6)]Dyn A(1-11)-NH2 led to an analogue with pronounced potency and selectivity enhancement for the mu opioid receptor, whereas cyclization between D-Asp(3) and Lys(7) in c[D-Asp(3),Lys(7)]Dyn A(1-11)-NH2 led to a potent ligand (IC(50) 4.9 nM) with kappa receptor selectivity [10].

Anatomical context of MOR

• The porcine mu opioid receptor: molecular cloning and mRNA distribution in lymphoid tissues [8].
• Here, we investigated the agonist-induced internalization of the mu opioid receptor (MOR) in vivo by using the guinea pig ileum as a model system and immunohistochemistry with an affinity-purified antibody to the C terminus of rat MOR [7].
• Some of these tests (opioid receptor binding assays, guinea pig ileal longitudinal muscle preparation, rat and mouse vas deferens preparation, acetic acid writhing antagonism test) indicate that 2 is a selective mu opioid receptor antagonist [11].
• The present study examined protein kinase A (PKA) and protein kinase C (PKC) involvement in the maintenance of cellular tolerance to mu opioid receptor agonists resulting from chronic opiate exposure in neurosecretory cells of the hypothalamic arcuate nucleus (ARC) [12].
• Mu opioid receptor activation reduces inhibitory postsynaptic potentials in hippocampal CA3 pyramidal cells of rat and guinea pig [13].

Associations of MOR with chemical compounds

• Unlike the kappa mediated actions, the mu opioid receptor agonist DAMGO inhibited Sprague-Dawley mossy fiber responses, as it does in guinea pig [14].
• Thus, estrogen binds to a specific receptor that activates PKA to rapidly uncouple the mu-opioid receptor from its K+ channel [15].
• The protein synthesis inhibitor cycloheximide did not block the estrogenic uncoupling of the mu-opioid receptor from its K+ channel, implying a nongenomic mechanism of action by E2 [15].
• The eight analogues of DPDPE showed highly variable binding and bioassay activities particularly at the delta opioid receptor (4 orders of magnitude), but also at the mu opioid receptor, which led to large differences (3 orders of magnitude) in receptor selectivity [16].
• Analogues of the potent and moderately mu-opioid-receptor-selective cyclic beta-casomorphin-5 derivative H-Tyr-c[-D-Orn-Phe-D-Pro-Gly-] (2) were prepared by conventional solution synthesis [17].

Other interactions of MOR

• The rate and degree of subsensitivity development to morphine (mu-opioid receptor, preferred, but not selective agonist) and U50488H (highly selective kappa-opioid receptor agonist) were assessed in vitro on guinea pig ileum (GPI) of cholestatic animals 2, 5, and 7 days after bile duct ligation [18].
• There was no cross-tolerance between kappa and mu opioid receptor agonists as measured with the in vitro electrophysiological assay, and the noncompetitive N-methyl-D-aspartate receptor antagonist MK801 did not prevent the development of tolerance to either the electrophysiological effects or the hypothermic effects of kappa opioids [19].

Analytical, diagnostic and therapeutic context of MOR

• METHODS: We used mu opioid receptor (muOR) internalization as a measure of opioid release with immunohistochemistry and confocal microscopy [20].
• Chronic sympathetic denervation entails subsensitivity to alpha(2)-adrenoceptor agonists and supersensitivity to kappa- and mu-opioid receptor agonists modulating cholinergic neurons in the guinea pig colon [21].

References