Lecture 10 - Pharm2210.pdf

Pharm 2210 lecture 10 Study online at https://quizlet.com/_dab878 1. Associated with one or more Gprotein receptors (metabotropic) metabolic steps 2. Why are G-protein receptors Because they involve the action of 1 or called metabotropic receptors more metabolic pa...

Pharm 2210 lecture 10 Study online at https://quizlet.com/_dab878 1. Associated with one or more Gprotein receptors (metabotropic) metabolic steps 2. Why are G-protein receptors Because they involve the action of 1 or called metabotropic receptors more metabolic pathways 3. Why are G-protein coupled re- Have 7 helical transmembrane domains ceptors "hepta helical" 4. G-protein coupled receptors Can be linked to ion channels Can generate second messengers Can cause protein phosphorylation 5. Receptor superfamily 4 major types of receptors Have similar transduction processes Similar general structures 6. How superfamilies are distin- HOW the signal is transduced guished NOT by what stimulates the receptor NOT on how the stimulation changes cell function 7. Largest superfamily G Protein coupled receptors 8. G protein receptor endoge- Neurotransmitters nous compounds Hormones Opioids Amines Peptides Proteins Light-sensitive compounds Odours 9. Interact with G protein recep- Heterotrimeric G proteins tors GTP- and GDP- binding proteins 10. Signal transduction pathways Adenylate cyclase linked to G protein receptors Phospholipase C Phosphodiesterase Ion channels 1/4  Pharm 2210 lecture 10 Study online at https://quizlet.com/_dab878 11. How G protein-coupled recep- Drug binds to G protein receptor> change tors work in cell function via intracellular G protein 12. 2 binding sites of G protein re- In membrane (N terminus) or extracellular ceptors (C terminus) 13. Enzymes or channels Effectors of G protein coupled receptors 14. Hormones or slow neurotrans- G protein. coupled receptors respond to mitters ___ (fast acting, seconds) 15. Adrenoceptors, muscarinic Examples of G protein coupled receptors aCh receptors 16. Salbutamol Beta-2 adrenoceptor agonist, relieves bronchospasm in asthma 17. Acetylcholine muscarinic agonist Activates phospholipase C 18. Noradrenaline and adrenaline Beta adrenoceptors bind and activate Alpha1 adrenoceptors Alpha2 adrenoceptors 19. Activates adenylate cyclase Activation of beta adrenoceptors (Gaq) 20. activates phospholipase C Alpha1 adrenoceptors (Gas) 21. inhibits adenylate cyclase Alpha2 adrenoceptors (ga1) 22. Three main classes of Galpha Gas - activates adenylate cyclase proteins Gaq - inhibits adenylate cyclase Gai - activates phospholipase C 23. activates adenylate cyclase Gas 2/4  Pharm 2210 lecture 10 Study online at https://quizlet.com/_dab878 24. inhibits adenylate cyclase Gai 25. activates phospholipase C Gaq - muscurunic acetylcholine receptors 26. Why do G protein receptors 3 types of G proteins in G protein domain "heterotrimeric" Galpha Gbeta Ggamma 27. protein kinases and phos Responsible for protein regulation 28. Protein kinases phosphorylate proteins (add P group), cause activation 29. protein phosphatases dephosphorylate proteins (take P group), deactivation 30. alpha subunit Binds GTP, has GTPase activity (binds GTP to form GDP) 31. Effector proteins which gener- G proteins link GPCRs to ate second messengers 32. (Gas) adenylate cyclase cAMP generated by 33. (Gaq) Phospholipase C Generates inositol 1,4,5- triphosphate & di- acylglycerol 34. Edogenous substance or drug 1st & 2nd messengers & cAMP Binding of first messenger generates 2nd 35. G protein signal transduction Agonist binds to receptor> activates g pro- pathway tein > activates effecter > activates active 2nd messenger > activates protein kinase > activated kinase causes response Cascade response 36. activation of G protein 3/4  Pharm 2210 lecture 10 Study online at https://quizlet.com/_dab878 Agonist activates receptor (causes confor- mational change), increase affinity of G protein 37. How Gprotein activation works Substance binds to receptor Receptor binds to g protein Binding > conform change in Ga GTP binds to Ga Ga catalyses exchange of GDP for GTP 38. activation of adenylate cyclase Ga dissociates from other G proteins Ga binds to adenylate cyclase Adenylate cyclase > cyclisation of ATP to cAMP GTP hydrolysed to GDP > Ga dissociates from Adenylate cyclase Ga returns to G proteins Receptor dissociates from G proteins> in- activation Agonist no longer binds > receptors returns to normal state 39. Smooth muscle relaxation Caused by activation of beta2-adrenocep- tors 40. smooth muscle contraction Caused by activation of Muscarinic acetyl- choline receptors 4/4