神经生物学 10-15-1ach神经递质 _wjj.pptVIP

Indirect methods： a. Measure of cholinesterase activity：Koelle, Friedenwald (1947) Acetylthiocholine (乙酰硫代胆碱法, AchE法）. b. ChAT: 1970’s, ChAT multiple colonial antibody;Eckenstein (1981) ChAT monoclonal antibody. Houser (1983): Consistence of AchE method and ChATmethod. SNAP-25 SYNTAXIN Synaptobrevin (VAMP) Botulinum toxin Tetanus toxin ?-bungarotoxin ?- bungarotoxin H+ vesamicol Transmitter is GLYCINE Transmitter is ACETYLCHOLINE Section III: Enzymatic decomposition and inactivation Specific cholinesterase (AchE) ：mainly in neural tissues。 Non- Specific cholinesterase (butyrylcholinesterase): glia cells, non-neural tissues. Chemical structure of AchE Anion site: imidazole group of histidine(组氨酸）. Site of Enzymatic decomposition: -OH of serine , nucleophilic I. Enzymatic decomposition and inactivation Life cycle of Ach （I）reversible Physostigmine, neostigmine: 为含季铵基团的氨基甲酸酯类。 Edrophonium: 依酚氯铵：含季铵基团，但无氨基甲酰基。起效快，作用短。 （II）irreversible : organic phosphorus pesticide, chemical warfare agent（VX, 沙林） II. Cholinesterase inhibitors Organophosphorous insecticides Anticholinesterases B A C D A 氯磷定(2-PAM·Cl)　B 双复磷(LüH-6)　C 甲磺磷定(P2S)　D 双磷定(TMB-4) Alzheimer’s disease 四氢氨基吖啶（tetrohydro aminoacridine antidotes to anticholinesterases symptomatic “antidote” - atropine pralidoxime (2-PAM) mode of action???? Section IV: Cholinergic Receptors I. Muscarinic receptor II. Nicotinic receptor N1 N2 Purification of cholinergic receptors Purification of receptors cDNA library Homology screening ???????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus 金环蛇 Bungarus fasciatus 银环蛇 Bungarus multicinctus 银环蛇 Bungarus multicinctus Pur