It is reported that tachyphylaxis has been displayed by many GPCRs (G-protein–coupled receptors). It is an intense loss of functional receptor response after rehashed stimuli with an agonist. GPCRs are essential clinical focuses for an array of problems. Subsequently, clarification of the ligand features that add to receptor tachyphylaxis and flagging occasions beneath this peculiarity is vital for drug finding and advancement. In this review, we analyzed the job of ligand-restricting energy in the tachyphylaxis of AT1R (angiotensin II sort 1 receptor) utilising bioluminescence resonance energy transmission tests to observe flagging occasions under both active and balance conditions. We explored AT1R signal transduction and movement advanced by the endogenous tachyphylactic agonist Ang II (angiotensin II) and its analogs, depicted already for initiating decreased receptor tachyphylaxis. Approximation of binding kinetic limits of the ligands uncovered that the residence time of Ang II was greater than that of the analogs, coming about in more sustained Gq protein activation and enrolment of β-arrestin than that stimulated by the analogs. Besides, we saw that Ang II prompted more supported internalisation of the receptor, along these lines impeding its reusing of the plasma membrane and forestalling further receptor reactions. These outcomes show that the obvious absence of tachyphylaxis in the analogs came about because of their short home time at the AT1R. Likewise, our information features the importance of total portrayal of novel GPCR drug applicants, considering their receptor binding kinetics also.
Reference:https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.121.17977
