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g. Overview of links between sections 9 to 13. From signal perception (by a GPCR) to response (28/11 -13). Starting point: GPCR & a/b/g complex. P.M. GDP. a. b. g. Ligand: e.g. fMet , adrenalin, “smell”, light, etc. P.M. GTP. GDP. b. a. a. +. b. g. GTP. GDP.
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g Overview of links between sections 9 to 13 From signal perception (by a GPCR) to response (28/11 -13) Starting point: GPCR & a/b/g complex P.M. GDP a b g Ligand: e.g. fMet, adrenalin, “smell”, light, etc. P.M. GTP GDP b a a + b g GTP GDP • The trimeric G-protein complex is recruited to the receptor • GDP/GTP exchange (the receptor acts as a GEF)
PLC-b Adenylyl cyclase Examples of down-stream GPCR effectors Organ specific GTP Most cells aolf GTP GTP GTP GTP as at aq ai ADRENALIN: cAMP synthesis in liver and muscle cells Protein kinase A SMELL: cAMPsynthesis in olfactory cells Ion channels LIGTH: cGMPhydrolysis in cells of the retina Ion channels cGMP-phospho- diesterase
Transmission of signals through CNS & PNS De-polarization or hyper-polarization (electrical signals) Synaptic signaling (electrical signals & neurotransmitters) : Electrical signal
Control of smooth muscle relaxation Default state = contraction Ca2+ : Electrical signal Acetylcholine (synaptic signaling) Endothelial cells produce NO Diffusion of NO to smooth muscle cells (paracrine signal) Activation of guanylylcyclase cGMP Activation of an “in ward” Ca2+ pump Decreased cytosolic [Ca2+] Actin-myosin filaments slides apart smooth muscle relaxation Increased blood flow Ca2+ Response = relaxation
Tropomyosin Tropomyosin Tropomyosin Tropomyosin Neuromuscular junction Somatic motor neurons project their axons to skeletal muscles. The interface between motor neurons and skeletal muscles is a specialized synapse termed neuromuscular junction. Acetylcholine release at the neuromuscular junction Depolarization of muscle cells (-70 mV ~0 mV) Opening of Ca2+channels Increased cytosolic Ca2+ Troponin mediated translocation of tropomyosin Response = contraction Ca2+
The Hypothalamic-Pituitary-Adrenal system Physical work/stress Two distinct signals to AG SNS signal GPCR (AG medulla): Adrenalin secretion into the blood GPCR (liver and muscles) adenylylcyclase cAMP Protein kinase A Glycogen phosphorylase Glycogen breakdown Neuroendocrine integration ACTH secretion GPCR (AG cortex): Cortisol secretion into the blood (lipolysis etc etc) AG:Adrenal Gland ACTH: AdrenoCorticoTropicHormone, SNS: Sympathetic Nervous System