1、第 4 章 傳出神經(jīng)系統(tǒng)藥理學(xué)概論Chapter 4 General Consideration of Drugs Affecting the Efferent Nervous System掌握傳出神經(jīng)系統(tǒng)受體的分類，各型受體激動時的生理效應(yīng)傳出神經(jīng)按遞質(zhì)的分類，主要遞質(zhì)（Ach和NE）的作用消失方式傳出神經(jīng)系統(tǒng)植物神經(jīng)運動神經(jīng)交感 NS副交感NS中樞神經(jīng)神經(jīng)元 效應(yīng)器NA骨骼肌AchAchAchAch傳出神經(jīng)系統(tǒng)的 遞質(zhì) 及受體 神經(jīng)沖動神經(jīng)末梢釋放遞質(zhì)（transmitter）突觸（synapse）下一級神經(jīng)元或效應(yīng)器的受體（receptor）生物效應(yīng)Fig. 4-1 Schematic

2、diagram of the efferent nerve system (ENS) and its related transmitters as well as receptors.傳出神經(jīng)按遞質(zhì)分類膽堿能神經(jīng)交感、副交感節(jié)前纖維(腎上腺髓質(zhì))副交感節(jié)后纖維運動神經(jīng)支配汗腺和骨骼肌血管舒張的交感神經(jīng)去甲腎上腺素能神經(jīng)大部分交感神經(jīng)節(jié)后纖維實線：節(jié)前纖維虛線：節(jié)后纖維藍色：膽堿神經(jīng)紅色：去甲腎上腺神經(jīng)第一節(jié) 遞質(zhì)與受體 遞質(zhì) 乙酰膽堿，Ach 去甲腎上腺素，NE 受體膽堿受體腎上腺素受體合成： 膽堿 +乙酰輔酶AAch膽堿乙酰化酶Ach儲存：神經(jīng)末梢囊泡內(nèi)釋放： 胞裂外排、量子化釋放 消失：

3、Ach 乙酸+膽堿膽堿酯酶合成：酪氨酸 多巴 多巴胺(進入囊泡) NA酪氨酸羥化酶多巴脫羧酶多巴胺-羥化酶儲存： 囊泡釋放： 胞裂外排作用消失：uptake 1 被神經(jīng)末梢攝取(75 % 90%)，再攝入神經(jīng)末梢囊泡中貯存uptake 2 被非神經(jīng)末梢攝取，被COMT和MAO滅活NE膽堿受體M受體M1-神經(jīng)節(jié)、腺體M2-心臟M3-平滑肌、腺體N受體N1-神經(jīng)節(jié)、腎上腺髓質(zhì)N2-骨骼肌 M受體激動效應(yīng)抑制循環(huán)：心率減慢，心肌收縮力減弱，血管擴張，血壓降低；興奮平滑?。褐夤?、胃腸道、泌尿道、子宮等平滑肌收縮；瞳孔縮?。和桌s肌收縮；腺體分泌增加：汗腺、支氣管腺、消化腺等的分泌增加。N受體激動效

4、應(yīng)N1受體激動效應(yīng) 植物神經(jīng)節(jié)興奮N2受體激動效應(yīng) 骨骼肌收縮腎上腺素受體受體-血管平滑肌1-突觸后膜2-突觸前膜受體1-心臟2-支氣管平滑肌、骨骼肌血管、冠狀動脈血管1激動效應(yīng)：血管收縮(血壓升高), 瞳孔開大。 突觸前膜上2激動效應(yīng)：負反饋抑制去甲腎上腺素釋放。1激動效應(yīng)：心臟興奮2激動效應(yīng)：支氣管平滑肌松弛，骨骼肌血管和冠狀血管舒張 突觸前膜上2激動效應(yīng)：正反饋調(diào)節(jié)去甲腎上腺素釋放多巴胺受體 （ dopaminergic receptor） D1 外周效應(yīng)器上的DA受體 D2 突觸前膜 DA受體：腎、腸系膜處血管舒張三、受體效應(yīng)偶聯(lián)機制 膽堿受體 M受體是G蛋白偶聯(lián)受體，受體活化可激活磷

5、脂酶C，產(chǎn)生IP3和DAG；亦可促進鉀通道開放或抑制鈣通道。 N受體是離子通道偶聯(lián)受體，被激動后，離子通道開放并產(chǎn)生效應(yīng) 。腎上腺素受體和受體均屬G蛋白偶聯(lián)受體家族。1受體活化通過激活磷脂酶C，使IP3和DAG產(chǎn)生增加；2受體活化，抑制腺苷酸環(huán)化酶，使cAMP產(chǎn)生減少；所有受體活化后，興奮腺苷酸環(huán)化酶，使cAMP產(chǎn)生增加. 第四節(jié) 傳出神經(jīng)藥物的基本作用及分類直接作用于受體 激動藥（ agonist) 阻斷藥（blocker)影響遞質(zhì) 釋放、轉(zhuǎn)化、儲存藥物分類（自學(xué)）Acetylcholine is synthesized from acetyl coenzyme A (acetyl CoA)

6、 and choline. Its action is terminated by acetylcholinesterase.The rate-limiting step in the synthesis of norepinephrine and epinephrine is the conversion of tyrosine to DOPA by tyrosine -hydroxylase.The effect of norepinephrine is terminated predominantly by reuptake into the neuron from which it w

7、as released.Cholinergic receptors include muscarinic receptors and nicotinic receptors.All autonomic ganglia have nicotinic receptors.All receptors at the neuromuscular junction are nicotinic receptors.All target organs of the parasympathetic nervous system have muscarinic receptors.Activation of ni

8、cotinic receptors results in muscle contractionIn the resting state (not in fight-or-flight situation), most dually innervated organs are controlled by the parasympathetic system.Adrenergic receptors include -adrenergic receptors and -adrenergic receptors. Each type also has its own subtypes.Remember : the sympathetic system is mediating the fight-or-flight response.Many organs are innervated by both the sympathetic and parasympathetic nervous systems. Most of the time the two systems have opposing effects.R