Disease relevance of OPRK1

• DADLE preconditioning significantly increased ischemia-induced arrhythmias relative to controls, whereas pentazocine-preconditioned animals (n = 2) experienced intractable ventricular fibrillation during ischemia. kappa-Opioid receptor blockade with DADLE or pentazocine preconditioning alleviated proarrhythmic effects [1].

Psychiatry related information on OPRK1

• The interaction between dynorphin and dopamine systems makes the kappa-opioid receptor a potential drug discovery target for the development of therapeutic agents for schizophrenia and drug abuse [2].

High impact information on OPRK1

• The kappa-opioid receptor from guinea pig brain exhibits a unique mobility on sucrose density gradient centrifugation but has not been characterized in purified form [3].
• These results suggest that the KOR1 protein is primarily, but not exclusively, deployed to postsynaptic membranes where it mediates the effects of products of preprodynorphin and possibly preproenkephalin [4].
• In sections from rat and guinea pig brain, prominent KOR1 staining was seen in the ventral forebrain, hypothalamus, thalamus, posterior pituitary, and midbrain [4].
• A subset of cells (29 of 83) were hyperpolarized by the kappa-opioid receptor agonist U69593 with an EC50 of 23 nM [5].
• The phosphorylation state of the kappa-opioid receptor was also elevated in brain slices from guinea pigs made tolerant to U50,488H by 5 days of continuous exposure and then maintained in kappa agonist to avoid acute opiate withdrawal [6].

Biological context of OPRK1

• Agonist-induced phosphorylation of the kappa-opioid receptor [6].
• A monoclonal antibody (mAb), KA8 that interacts with the kappa-opioid receptor binding site was generated [7].
• In guinea pig ileum preparations, 4e was characterized as a selective full agonist at the kappa opioid receptor (IC50 = 2.8 nM); while its beta-isomer 4f was a partial agonist (78% at 1 microM), with antagonist activity observed at both mu- and kappa-opioid receptors [8].
• The kappa-opioid receptor agonists including U-50,488H and dynorphin A (1-17) in ranges of 0.1-100 nM inhibited the hydrolysis of GTP to GDP (P(i) release) inherent in GTP-binding proteins (G proteins) in guinea pig cerebellar membranes [9].
• Viewed collectively, these results provide further evidence for heterogeneity of the kappa opioid receptor, which may provide new targets for drug design, synthesis, and therapeutics [10].

Anatomical context of OPRK1

• We have previously shown that kappa opioid receptor-like immunoreactivity (KT-LI) is present in axons and terminals in the granule cell layer and inner molecular layer of the guinea pig dentate gyrus [11].
• Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery [12].
• Kappa opioid receptor tolerance in the guinea pig hippocampus [13].
• 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 [14].
• IMPLICATIONS: Our results indicate that delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available intracellular Ca(2+) concentrations in intact isolated guinea pig beating hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation [15].

Associations of OPRK1 with chemical compounds

• The results of this study show that the kappa-opioid receptor was phosphorylated in an agonist-dependent manner in brain slices taken from untreated and U50,488H-tolerant animals [6].
• Kappa opioid receptor-like immunoreactivity is present in substance P-containing subcortical afferents in guinea pig dentate gyrus [11].
• Asimadoline (EMD 61753) is a peripherally selective kappa-opioid receptor agonist which is under development as a therapeutic analgaesic [16].
• The racemic compound (+/-)-BW373U86 ¿(+/-)-4-((alpha R*)- alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxy- benzyl)-N,N-diethylbenzamide dihydrochloride¿ is a potent delta opioid receptor agonist in the mouse vas deferens assay with little mu or kappa opioid receptor activity in the guinea pig ileum tissue preparation [17].
• Pharmacological properties of R-84760, a novel kappa-opioid receptor agonist [18].

Other interactions of OPRK1

• On the other hand, [Cys8,Cys13]Dyn A1-13-NH2 and [D-Cys8,D-Cys13]Dyn A1-13-NH2 (5) display high kappa potencies and selectivities at the peripheral (GPI) but not at the central (GPB) kappa opioid receptor [19].

Analytical, diagnostic and therapeutic context of OPRK1

• The mAb KA8 purified by affinity chromatography on protein A-Sepharose CL4B was able to precipitate the antigen from a solubilized and affinity-purified frog brain kappa-opioid receptor preparation [7].
• Immunoprecipitation of the kappa receptor from guinea pig hippocampal slices preincubated in [32P]orthophosphoric acid revealed a basal phosphorylation of the kappa-opioid receptor [6].
• RT-PCR revealed the expression of mu-, delta- and kappa-opioid receptor mRNAs in cultured adrenal chromaffin cells [20].
• AIM: To study the effect of nociceptin (NC), a newly discovered heptadecapeptide, and U-50488H, a kappa-opioid receptor agonist, on excitatory non-adrenergic non-cholinergic (eNANC) constriction responses in guinea pig isolated bronchus [21].

References