Exam 3 - Lec 1, Neuropharm NE, 5-HT & HA, Neuropharm muscarinic Ach and DA receptors, Neuropharm Nicotinic Ach Receptors, nAChRs (nicotine acetlycholine receptors) DRUGS, mAChR ligands, Neuropharmacology (PhD), Thompson - Spring 2016 UTD, Norepinephrine

Exam 3 - Lec 1, Neuropharm NE, 5-HT & HA, Neuropharm muscarinic Ach and DA receptors, Neuropharm Nicotinic Ach Receptors, nAChRs (nicotine acetlycholine receptors) DRUGS, mAChR ligands, Neuropharmacology (PhD), Thompson - Spring 2016 UTD, Norepinephrine mGluRs - Structure -Answer-Homodimers Homodimers have ____ sets of ____ transmembrane segments -Answer-2, 7 What is the Hill coefficient for Glu? -Answer-1 Receptors in Class I of mGluRs? -Answer-mGluR 1 & 5 Receptors in Class II of mGluRs? -Answer-mGluR 2 & 3 Receptors in Class III of mGluRs? -Answer-mGluRs 4-8 Which class produces excitatory effects? -Answer-Class I Which class produces inhibitory effects? -Answer-Class II & III Class I receptors acts upon ____ receptor, increasing ____ (both intracellularly and from stores) -Answer-IP3, Calcium Class I receptors activate what membrane bound enzyme, resulting an increase in Phosphoglycerol? -Answer-Phosholipase C Class II Rs act on enzyme ________, decreasing cAMP. -Answer-Adenylyl Cyclase In the Hippocampus, mGluR1 is rare in ____ pyramidal neurons & abundant in ____ pyramidal neurons and granular cells -Answer-CA1, CA3 What two Rs in Class III are abundantly expressed in the hippocampus? -Answer- mGluR 5 & 6 In the Cerebellum, Purkinje cells only express _____ Rs -Answer-mGluR 1 mGluRs are involved in what 4 attributes? (Think PMLB) -Answer-Perception of pain, Mood/affect (especially anxiety), Learning/memory, Blood Flow/Headaches mGluRs are involved in the modulating the activity of Transmitter Release and what three types of channels? -Answer-Voltage - dependent ion channels, Calcium - dependent ion channels & Ligand - gated ion channels Class I Rs act through which type of g protein? -Answer-Gq Draw the Class I effector mechanism, starting from Glutamate and ending with the enzymes it affects. -Answer-- Group I's are mGluR 1 /5 which are acted upon by glutamate, which act through Gq's, which activate Phospholipase C activity, whose substrate is PIP2 and products are IP3 and Diacylglycerol (DAG). - IP3 activate/acts as agonist for IP3-R which releases calcium. DAG acts as activator of PKC. What are the 4 types of Agonists for Class I Ligands? (Think GIDAQ) & which one is endogenous/"found in mushrooms", which one is exogenous & which one is used experimentally -Answer-Glutamate, Ibotenic Acid, DHPG, ACPD, Quisqualate Glu, Ibotenic acid DHPG What is an antagonist of Class I ligands? -Answer-CPG Class I agonists cause excitation through alpha or beta/gamma subunits? -Answer- Alpha What are 2 hypotheses for how alpha subunits increase excitability (this results in a seizure if it happens in the brain) ? -Answer-1) Phosphorylation of VDCCs could decrease Ca2+ influx, reducing Inhibitory AHP 2) Reduced Ca2+ influx What are 2 ways alpha subunits alter excitability? -Answer-Effect mediated by PKC activated by DAG, or CAMKII mediated effect activated by IP2 receptor. Presynaptically, alpha-subunit caused phosphorylation leads to ______ Ca flow through NMDARs. Postsynaptically, VDCCs get phosphorylation and ________ Ca into the cell. -Answer-increase, decrease Class I agonists can decrease neurotransmitter release by ______ presynaptic calcium -Answer-decreasing ______ cells regulate blood flow/ headaches. -Answer-Glial Class I agonists can cause headaches by stimulating glial cells, which results in a cascade of what enzyme? -Answer-PLA (phospholipase A) Draw the Class II & III effector mechanism, starting from Glutamate and ending with the enzymes it affects. -Answer-Glu -- mGluR2//3 & mGluR4-8 -- Gi (downregulates AC activity; inhibits it so less ATP burned up and less cAMP produced as product and so then also downregulated PKA activity, meaning whatever PKA was going to phosphorylate, there is less of that substance) -- AC -- (which is then converted via ATP to) -- cAMP -- PKA Class II agonists on __________ terminals can enchance Glu release -Answer- presynaptic What are the 4 types of class II agonists? (Think GNAD) -Answer-Glu, NAAG, APDG, DCG What are the 4 types of class II antagonists? (Think EMA) -Answer-Ethyl Glutamate, MCPG, ADED What are the 2 types of class III agonists? -Answer-Glu, AP4 What is a class III antagonist? -Answer-MAP4 befloxaton -Answer-reversible, A-specific (NE, 5-HT) MAO-I inhibitor NE degradation inhibitor harmaline -Answer-irreversible, A specific (NE, 5-HT) MAO-I inhibitor NE degradation inhibitor Ipronazid -Answer-irreversible A or B nonspecific MAO-I inhibitor NE degradation inhibitor Deprenyl -Answer-irreversible, B specific (DA, HA) MAO inhibitor NE degradation inhibitor Tolcapone -Answer-irreversible COMT inhibitor NE degradation inhibitor DA -Answer-non selective agonist for all alpha 1 adrenoceptors NE -Answer-non selective agonist for all alpha 1 adrenoceptors Epi -Answer-non selective agonist for all alpha 1 adrenoceptors tetrahydrazoline -Answer-selective agonist for alpha 1A adrenoceptors phenylephrine -Answer-non selective agonist for all alpha 1 adrenoceptors ephederine -Answer-non selective agonist for all alpha 1 adrenoceptors pseudoephederine -Answer-non selective agonist for all alpha 1 adrenoceptors