Receptor bias: difference between revisions
Diff·revision 8 → 9·20:32, 26 Dec 2024
Difference between revision 8 and revision 9 of Receptor bias. 6 lines changed; the page grew by 727 bytes.
| Revision 8 — 17:08, 4 Dec 2024 Chromatokid (talk) convert the receptor-distribution list to a table 2,387 bytes ±0 | Revision 9 — 20:32, 26 Dec 2024 CustomsClarke (talk) add the citation for the co-secretion finding 3,114 bytes +727 | ||
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| 19 | The concept is real and well supported at the level of receptor conformation. What is contested is whether measured bias predicts anything clinically.{{r|jones2018}} | 19 | The concept is real and well supported at the level of receptor conformation. What is contested is whether measured bias predicts anything clinically.{{r|jones2018}} |
| 20 | 20 | ||
| + | 21 | == At the GLP-1 receptor == | |
| + | 22 | An agonist producing sustained cAMP with reduced β-arrestin recruitment internalises the receptor less and maintains surface expression, which might sustain insulin secretion better over prolonged exposure. This is the therapeutic hypothesis.{{r|jones2018}} | |
| + | 23 | ||
| + | 24 | Evidence in humans is indirect. The bias factors reported for marketed agonists have not been shown to predict clinical differences between them, and the clinical differences that exist are adequately explained by pharmacokinetics and dose.{{r|drucker2018}} | |
| + | 25 | ||
| 21 | == References == | 26 | == References == |
| 22 | {{reflist}} | 27 | {{reflist}} |
| 23 | <ref name="jones2018">Jones B, Buenaventura T, Kanda N, et al. "Targeting GLP-1 receptor trafficking to improve agonist efficacy." ''Nature Communications'' 9:1602 (2018). PMID 29686245.</ref> | 28 | <ref name="jones2018">Jones B, Buenaventura T, Kanda N, et al. "Targeting GLP-1 receptor trafficking to improve agonist efficacy." ''Nature Communications'' 9:1602 (2018). PMID 29686245.</ref> |
| 24 | <ref name="kenakin2013">Kenakin T, Christopoulos A. "Signalling bias in new drug discovery: detection, quantification and therapeutic impact." ''Nature Reviews Drug Discovery'' 12(3):205–216 (2013). PMID 23411724.</ref> | 29 | <ref name="kenakin2013">Kenakin T, Christopoulos A. "Signalling bias in new drug discovery: detection, quantification and therapeutic impact." ''Nature Reviews Drug Discovery'' 12(3):205–216 (2013). PMID 23411724.</ref> |
| + | 30 | <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> | |
| 25 | 31 | ||
| 26 | {{DEFAULTSORT:Receptor bias}} | 32 | {{DEFAULTSORT:Receptor bias}} |