PCL302H1 Lecture Notes - Lecture 11: G Protein–Coupled Receptor, Pharmacodynamics, Clathrin
11 Oct 2016
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Lecture 11: inhibition and desensitization pathways: mechanisms of pathology. Following activation of gpcrs, they are inactivated by multi-step mechanism, and the activation of g proteins are inactivated by increasing gtpase activity. Also the 2nd-messenger regulated kinase can inhibit active/ and inactive receptors. Note: all these processes contribute to inactivation and desensitization mechanisms, making the cell temporarily less responsive to stimulation. Happens when agonist is at high concentration (prolonged exposure), the receptor is uncoupled from its cascade. General: stimulate r signals stimulate r again decrease signaling by interfere gpcr decrease downstream signaling. Grk binds to phosphorylated gpcr at c-term, then recruits arrestins (for desensitization) Ap2 and clathrin recruited to site, clathrin starts pinching off the membrane, internalizes gpcr and translocate it to early endosome. Receptor can get degraded or all parts gets recycled. Camk, pkc) can also phosphorylate gpcr and may go through same process. Happens when repeated stimulation by an agonist. Gpcr activates gai inhibit ac no camp production.
