Pharmacology of efferent nervous system Cholinergic Pharmacology Adrenergic Pharmacology 2
• Cholinergic Pharmacology • Adrenergic Pharmacology Pharmacology of efferent nervous system 2
AC ACh N Parasympathetic Medulla Cardiac and smooth muscle gland cells, nerve terminals Sympathetic ACh Sweat glands ACh NE Sympathetic Cardiac and smooth muscle gland cells, nerve terminals Spinal ACh Sympathetic Renal vascular smooth muscle ACh Epi, NE ACh Adrenal medulla Somatic Skeletal muscle Voluntary motor nerve Copyright @2006 by The McGraw-Hill Companies, Inc. All rights reserved
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NE synthesis in nerve terminals and turnover 1 SYNTHESIS OF NH2 NOREPINEPHRINE CH.C-COOH he rate-limiting step 2 UPTAKE INTO STORAGE VESICLES H Inactive 4 e Dopamine entera vesicle L-Tyrosine e Norepinephrine is protected Tyrosine hydroxylase om degradation in erin, o Transport into vesicle is HO Inactive HO CH2C-COOH L-DOPA 3 RELEASE OF NEUROTRANSMITTER DOPA decarboxylase coll membrane ( Pyridoxal phosphate) e Release blocked by HO HO 5 REMOVAL OF NOREPINEPHRINE Dopamine rapidly taken into neuron Dopamine B-hydroxylase cocaine and imlpram (Ascorbate, O) 4 BINDING TO RECEPTOR of neurotransmitter 一CHCH2NH2 SYNAPTIC Norepinephrine 6 METABOLISM SPACE Catecholamine Biosynthetic Pathway mIne oxidase INTRACELLULAR RESPONSE
NE synthesis in nerve terminals and turnover Catecholamine Biosynthetic Pathway 4
NH2 Norepinephrine and Epinephrine CH2C-COOH L-Tyrosine Synthesis in the Adrenal Medulla Tyrosine hydroxylase (Tetrahydrobiopterin, O,) PNMT苯氨基乙醇N-甲基转移酶 is located in the NH2 CH2C-COOH cytosol L-DOPA DBH多巴脱羧酶 is located in vesicles DOPA decarboxylase EPl is stored in vesicles EPl(-80%)and NE(-20%)are released into blood CH, CH NH Dopamine Dopamine B-hydroxylase PNMI NE)→NE一→EPI→EPI (Ascorbate, O2 H CHCH2 NH2 Norepinephrine Chromaffin cell Phenylethanolamine N-methyltransferase (S-adenosylmethionine CHCH NHCH Epinephrine
Norepinephrine and Epinephrine Synthesis in the Adrenal Medulla - PNMT苯氨基乙醇N-甲基转移酶 is located in the cytosol - DBH 多巴脱羧酶 is located in vesicles - EPI is stored in vesicles. - EPI (~80%) and NE (~20%) are released into blood Chromaffin cell NE PNMT NE EPI EPI 5
Norepinephrine and epinephrine Metabolism MAO B2b28-=b MHPG(3甲氧4羟苯乙二醇 CH2-NH2 -CH2 was used as an index of cns ne turnover Norepinephrine DOPGAL Epinephrine but generated mostly from aldehyde COMT aldehyde reducts COMT periphery CH,O VMA(香草扁桃酸) sometimes used as an index of ne turnover Normetanephrine DOPEG DOMA Metanephrine Sulfate conjugates COMT COM also prevalent Elimination by kidneys MOPEG or MHPG VMA VMA Urine MHPG-SO NMN-SO reductase dehydrogenase MN-SO MAO Relative amounts excreted MOPGAL
Norepinephrine and Epinephrine Metabolism MHPG (3-甲氧4-羟苯乙二醇): was used as an index of CNS NE turnover but generated mostly from periphery VMA(香草扁桃酸): sometimes used as an index of NE turnover Sulfate conjugates also prevalent or MHPG 6