Nervous System
(Anatomy, Physiology, Cell biology, Biochemistry, and Pharmacology)

NS	
	→Central NS
		→Brain
		→Spinal Cord
	→Peripheral NS
		→Somatic
		→Autonomic
			→Sympathetic
			→Parasympathetic
*The preganglionic neuron originates in the CNS; it forms synapse with the postgangionic neuron which locates its cell body in ganglia. All preganglionic neurons release acetylcholine as their transmitter.
*Sympathetic system is catabolic; the ganglia are located lateral to the vertebral column in the thoracic and lumber regions. Most of the sympathetic system utilizes norepinephrine.
*Parasympathetic system is anabolic; the ganglia are located closer to the target organs. All of the parasympathetic postganglinic fibers release acetylcholine.

Cholinergic Synapses

Cholinergic Synapses

˙Docking and Exocytosis of ACh

1. ACh molecules aew stored in neurosecretory vesicles in the terminal bulbs.
2. A nerve pulse from presynaptic axon opens the voltage-gated calcium channels in the terminal bulbs.
3. Elevated cytosolic calcium levels stimulate secretion.
　(a) Phosphorylation of synapsin in the membrane of neurosecretory vesicles that the vesicles no longer binds to the cytockeleton.
　(b) Rapid docking and fusion of neurosecretory vesicles with the plasma membrane in the terminal bulbs.
4. Docking at the active zone within the presynaptic neuronal membrane.

SNARE Hypothesis to
Neurosecretory Vesicles Docking

Synaptic Docking

Mechanism and Function

Homologue of SNARE model
Rab 3A Neuro-specific GTP-binding protein
Vesicle traffic controlling		 Rab GTPase
VAMP
(Synaptobrevin) 		v-SNARE
Syntaxin t-SNARE
SNAP25 Disassociation of VAMP from T-SNARE after fusion SNAP
Synaptotagmin Calcium-sensing protein
Block binding to neurexin-syntaxin compllex without Calcium		 (t-SNARE)

˙Acetylcholine Receptor

Cholinergic agonists

Ester:
Bethanechol: Urinary retention

Alkaloids:
Pilocarpine/生物鹼: 降低眼壓，治青光眼

筆記：藥理 or 副作用？
Muscarnergic agonists→平滑肌收縮
- Contraction of gallbladder' urinary bladder
- Constriction of pupil' bronchioles
- Increasing digestive tract activity
- Pancreas exocrine secretion, sweating, insulin and glucagon secretion
→ Salivation, GI distress and cramps(絞痛)

Cholinergic antagonists

Atropin/癲茄鹼: Muscarinic(/parasympathetic) antagonist; preoperatively reducing secretions
→止汗，散瞳，......

Scopolamine/hyoscine: prevent motion sickness
Oxybutynin: For urinary frequency increasing

Neuromuscular blockers:
- Succinylcholine: 肌肉鬆弛劑
- Botulinum Toxin: 肉毒桿菌毒素
- Tubocurarine: 箭毒
- Cobretoxin: 蛇毒
考古題：（題組）
1. Botulinum toxin is a depolarizing neruomuscular blocker.[True or false]
2. Oxybutynin, a muscarinic antagonist, is used for urinary frequency caused by bladder overactivity.[True or false]
3. Succinylcholine blocks the release of acetylcholine at all cholinergic synapses.[True or false]
4. Scopolamine is a cholinergic antagonist.[True or false]

˙Acetylcholinesterase

Irreversible inhibitors

Organophosphate/農藥: 傷腦筋(lipid solubility thus can cross blood-brain barrier)，支氣管收縮與窒息
→ Parathion/巴拉松
→ Sarin/麻原彰榥專用
Pralidoxime(2-PAM) and Atropine 可修復受損之cholinesterase

Reversible inhibitors

Same side effects as the direct cholinergic agonists.
→ Fasciculations/過收縮麻痺

可影響Neuromuscular junction(nicotinic)
Pyridostigmine and neostigmine: Treatment of Myasthenia gravis

手術後回復用藥(tubocurarine亦可)

考古題：（題組）
5. Organophospates such as sarin are often used to improve the muscle strength in patients with myasthenia gravis.[True or false]
6. The reversible cholinesterase inhibitors such as neostigmine are used in the treatment of open-angle glaucoma.[True or false]

考古題：Use the examples in the following list in classifying (分類) the cholinergic agonists. (pilocarpine; bethanechol; physostigmine; parathion; muscarine) (10%)

Adrenergic Synapses

Adrenergic receptor
	B1	Heart
	B2	Skeletal muscle blood vessels
		Bronchial smooth muscle	Lung
			Digestive track
			Urinary bladder
			Eye(ciliary muscle for遠視與散瞳/mydriasis)
	B3	Adipose tissue (fat stores)
		Liver (glycogen stores)

Monoamine oxidase(MAO) and catechol-o-methyl-transferase(COMT):
Norepinephrine incativation in the liver and brain.
考古題：The major pathway for the termination of the action of norepinephrine is _
NE → methoxyhydroxymandelic acid

Blood vessels dilation, galbladder and urinaty bladder relaxation, glucose and fatty acids released, ......
Blood pressure and peripheral resistance controlling
(a receptors→vasoconstriction → 血壓上升)

Adrenergic agonists

Ephinephrine: Localized bleeding control
筆記：牙科阻麻醉劑擴散用
Norepinephrine(relatively lowaffinity forβ2 receptors): Nasal decongestant(local application of a basoconstrictor)
筆記：治療鼻塞用

Dopamine: Renal and coronary vasodilation

Adrenergic antagonists

a-blockers: Vasodilation and hypertention treatment
筆記：比較具有專一性﹔B-blockers就會到處亂打，副作用高。

β-blockers: Cardiac arrhythmias(心肌梗塞), angina(心律不整) and hypertension management
Propanolol

Indirect-acting agents

Stored norepinephrine releasing
Amphetamine(methylphenidate): Attention deficit hyperactivity disorder in childern treatment.
Isoproterenol: Peripheral resistance decreasing and increase in heart rate and cardiac output.

Norepinephrine reuptake inhibitor
Reserpin/蛇根鹼
Cocaine
筆記：作用於Uptake 1 ，為中樞神經用之回收，不經過COMT 與MAO的作用。