ELIZA

return kwic search for showed out of >500 occurrences
663834 occurrences (No.9 in the rank) during 5 years in the PubMed. [cache]

338) These structurally diverse NOP agonists also showed differential receptor phosphorylation profiles at the phosphosites we examined and induced varying levels of receptor internalization.

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PMID:33958480 DOI:10.1124/molpharm.120.000076

2021 Molecular pharmacology

* Differential In Vitro Pharmacological Profiles of Structurally Diverse Nociceptin Receptor Agonists in Activating G Protein and Beta-Arrestin Signaling at the Human Nociceptin Opioid Receptor.

- Agonists at the nociceptin opioid peptide receptor (NOP) are under investigation as therapeutics for nonaddicting analgesia, opioid use disorder, Parkinson's disease, and other indications. NOP full and partial agonists have both been of interest, particularly since NOP partial agonists show a reduced propensity for behavioral disruption than NOP full agonists. Here, we investigated the in vitro pharmacological properties of chemically diverse NOP receptor agonists in assays measuring functional activation of the NOP receptor such as guanosine 5'-O-[gamma-thio]triphosphate (GTPγS) binding, cAMP inhibition, G protein-coupled inwardly rectifying potassium (GIRK) channel activation, phosphorylation, β-arrestin recruitment and receptor internalization. When normalized to the efficacy of the natural agonist nociceptin/orphanin FQ (N/OFQ), we found that different functional assays that measure intrinsic activity produce inconsistent levels of agonist efficacy, particularly for ligands that were partial agonists. Agonist efficacy obtained in the GTPγS assay tended to be lower than that in the cAMP and GIRK assays. These structurally diverse NOP agonists also showed differential receptor phosphorylation profiles at the phosphosites we examined and induced varying levels of receptor internalization. Interestingly, although the rank order for β-arrestin recruitment by these NOP agonists was consistent with their ability to induce receptor internalization, their phosphorylation signatures at the time point we investigated were not indicative of the levels of β-arrestin recruitment or internalization induced by these agonists. It is possible that other phosphorylation sites, yet to be identified, drive the recruitment of NOP receptor ensembles and subsequent receptor trafficking by some nonpeptide NOP agonists. These findings potentially help understand NOP agonist pharmacology in the context of ligand-activated receptor trafficking. SIGNIFICANCE STATEMENT: Chemically diverse agonist ligands at the nociceptin opioid receptor G protein-coupled receptor showed differential efficacy for activating downstream events after receptor binding, in a suite of functional assays measuring guanosine 5'-O-[gamma-thio]triphosphate binding, cAMP inhibition, G protein-coupled inwardly rectifying protein channel activation, β-arrestin recruitment, receptor internalization and receptor phosphorylation. These analyses provide a context for understanding nociceptin opioid peptide receptor (NOP) agonist pharmacology driven by ligand-induced differential NOP receptor signaling.

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[frequency of next (right) word to showed]

(1)197 that	(10)5 higher	(19)3 moderate	(28)2 large
(2)50 a	(11)5 significantly	(20)3 more	(29)2 lower
(3)23 the	(12)4 differential	(21)3 mostly	(30)2 reduced
(4)14 no	(13)4 greater	(22)3 promising	(31)2 remarkable
(5)12 an	(14)4 positive	(23)2 clinically	(32)2 similar
(6)11 significant	(15)3 better	(24)2 efficacy	(33)2 stereoselectivity
(7)6 good	(16)3 extensive	(25)2 hypersensitivity	(34)2 strong
(8)6 high	(17)3 how	(26)2 impairments
(9)5 elevated	(18)3 low	(27)2 increased

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--- WordNet output for showed --- Overview of verb show The verb show has 12 senses (first 11 from tagged texts) 1. (136) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (63) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (57) testify, bear witness, prove, evidence, show -- (provide evidence for; "The blood test showed that he was the father"; "Her behavior testified to her incompetence") 4. (43) show -- (make visible or noticeable; "She showed her talent for cooking"; "Show me your etchings, please") 5. (32) picture, depict, render, show -- (show in, or as in, a picture; "This scene depicts country life"; "the face of the child is rendered with much tenderness in this painting") 6. (24) express, show, evince -- (give expression to; "She showed her disappointment") 7. (24) indicate, point, designate, show -- (indicate a place, direction, person, or thing; either spatially or figuratively; "I showed the customer the glove section"; "He pointed to the empty parking space"; "he indicated his opponents") 8. (11) show, show up -- (be or become visible or noticeable; "His good upbringing really shows"; "The dirty side will show") 9. (7) read, register, show, record -- (indicate a certain reading; of gauges and instruments; "The thermometer showed thirteen degrees below zero"; "The gauge read `empty'") 10. (6) show -- (give evidence of, as of records; "The diary shows his distress that evening") 11. (2) usher, show -- (take (someone) to their seats, as in theaters or auditoriums; "The usher showed us to our seats") 12. show -- (finish third or better in a horse or dog race; "he bet $2 on number six to show") --- WordNet end ---