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• W2104631706 endingPage "514" @default.
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• W2104631706 abstract "In this study, we have compared the abilities of orexin-A and orexin-B and variants of orexin-A to activate different Ca²⁺responses (influx and release) in human OX₁ and OX₂ receptor- expressing Chinese hamster ovary cells. Responses mediated by activation of both receptor subtypes with either orexin-A or -B were primarily dependent on extracellular Ca²⁺, suggesting similar activation of Ca²⁺influx as we have previously shown for orexin-A and OX₁receptors. Amino acid-wise truncation of orexin-A reduced its ability to activate OX₁ and OX₂ receptors, but the response mediated by the OX₂ receptor was more resistant to truncation than the response mediated by the OX₁ receptor. We also performed a sequential replacement of amino acids 14 to 26 with alanine in the truncated orexin-A variant orexin-A_14–33. Replacement of the same amino acids produced a fall in the potency for each receptor subtype, but the reduction was less prominent for the OX₂ receptor. The most marked reduction was produced by the replacement of Leu20, Asp25, and His26 with alanine. Interestingly, extracellular Ca²⁺ dependence of responses to some of the mutated peptides was different from those of orexin-A and -B. The mutagenesis also suggests that although the determinants required from orexin-A for binding to and activation of the receptor are highly conserved between the orexin receptor subtypes, the OX₂receptor requires fewer determinants. This might in part explain why orexin-B has the affinity and potency equal to orexin-A for this subtype, although it has 10- to 100-fold lower affinity and potency for the OX₁ receptor." @default.
• W2104631706 created "2016-06-24" @default.
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• W2104631706 date "2003-01-24" @default.
• W2104631706 modified "2023-10-16" @default.
• W2104631706 title "Distinct Recognition of OX₁ and OX₂Receptors by Orexin Peptides" @default.
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• W2104631706 doi "https://doi.org/10.1124/jpet.102.048025" @default.
• W2104631706 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12606634" @default.
• W2104631706 hasPublicationYear "2003" @default.
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