L8: Parasympathetic system

Receptors and enzyme

Nicotinic recpetor

• location

  • parasympathetic and sympathetic ganglion

  • skeletal neuromuscular junction

  • Brain

• Features

  • consist of 3 subunits: α, β, δ

  • different selectively and response to pharmacological agents

  • ligand-gated ion channel

    • response: increased cation permeability

  • stimulated by acetylcholine and nicotine

Muscarinic receptors

• M1

  • located at CNS and salivary gland

  • CNS excitation, memory and salivary excretion increase when stimulated

• M2

  • located at heart

  • decrease heart rate, contractility and AV conduction when stimulated

• M3

  • located at smooth muscle, exocrine glands and eye

  • contract all smooth muscles (except blood vessel), increase glandular secretion and allow ocular accommodation when stimulated

Acetylcholinesterase (ACE)

• consists of two regions

  • anionic site: bind to basic moiety of ACh

  • esteratic site

• hydrolyse ACh rapidly

• high turnover rate

Drugs enhancing parasympathetic transmission

Nicotinic receptor agonist (not used clinically)

• Effect

  • enhance both the neurotransmission in parasympathetic and sympathetic

  • some sites sympathetic activation may predominate, but some parasympathetic

  • in higher dosage: affect neuromuscular junction and brain

  Tissue	predominant system	effect
  blood vessel	sympathetic	vasoconstriction
  heart	parasympathetic	bradycardia
  iris	parasympathetic	contraction
  ciliary muscle	parasympathetic	contraction
  bronchial muscle	parasympathetic	bronchoconstriction and increase secretion
  GI tract	parasympathetic	increase peristalsis and secretion
  urinary bladder	parasympathetic	contraction of detrusor and relaxation of sphincter
  salivary gland	parasympathetic	increase saliva secretion
  sweat gland	sympathetic	increase sweat secretion

  • neuromuscular junction: depolarisation → skeletal muscle tension or contraction

  • CNS: induces tremor, emesis, stimulate respiratory centre, convulsion

• Examples

  • Nicotine: not specific→ affect many other organs

  • lobeline

  • epibatidine

Anticholinesterase drug

• Mechnism

  • inhibit ACE to increase ACh activity at all cholinergic postganglionic synapses

  • increase activities of parasympathetic and sympathetic systems, neuromuscular junction and brain

• Examples

  • neostigmine and pyridostigmine

    • affect neuromuscular junction more significantly

    • treat myasthenia gravis

  • non-clinical use

    • pesticide

    • weapon

• Anticholinesterase poisoning

  • Dyflos, Sarin and VX: phosphorus compounds: long acting inhibitors of ACE

  • effect

    • bradycardia

    • hypotension

    • bronchoconstriction

    • convulsion

    • depression

  • Antidote: pralidoxime

    • contain an oxime group to lure phosphate group away from esteratic site of ACE

Muscarinic receptor agonist

• effects

  • heart

    • reduce heart rate and decrease contractility

    • result in blood pressure decrease

  • smooth muscles

    • all smooth muscle contraction except blood vessel

    • indirect relaxation effect on blood vessel via nitric oxide

  • exocrine glands

    • increase all secretion

    • ★ combine effect of bronchoconstriction and secretion may interfere breathing

  • eye

    • ciliary muscle contraction

      • lens becomes thicker to accommodate near vision

    • constriction of pupils: reduce amount of light entering eyes

    • improve drainage of aqueous humor to canal of Schelemm to reduce intraocular pressure

• Examples

  • Bethanechol

    • treat bladder and GI hypotonia

  • pilocarpine

    • treat glaucoma by regulating intraocular pressure

    • administration: eyedrop

  • cevimeline——selective M3 agonist

    • treat Sjogren syndrome by increasing salivary and lacrimal secretion

Drugs inhibiting parasympathetic transmission

Nicotinic receptor antagonist

• effect

  • inhibit sympathetic, parasympathetic systems, neuromuscular junction and brain

  • sine are selective to the receptor in neuromuscular junction only

  Tissue	predominant system	effect
  blood vessel	sympathetic	vasodilation
  heart	parasympathetic	tachycardia
  iris	parasympathetic	relaxation
  ciliary muscle	parasympathetic	relaxation→ X accomodate near vision
  bronchial muscle	parasympathetic	bronchodilation and decrease secretion
  GI tract	parasympathetic	decrease peristalsis and secretion
  urinary bladder	parasympathetic	urinary retention
  salivary gland	parasympathetic	decrease saliva secretion
  sweat gland	sympathetic	decrease sweat secretion

• Examples

  • botulinum toxin and β-bungarotoxin

    • poisoning may lead to parasympathetic and motor paralysis

    • local injection for cosmetic use

      • reduce wrinckles

    • treat blepharospasm, urinary incontinence and hyperhydrosis

Muscarinic receptor antagonist

• effect

  • heart

    • increase heart rate and contractility

  • smooth muscles

    • all smooth muscle contraction except blood vessel

  • exocrine gland

    • all exocrine secretion inhibition

    • slight reduction in GI tract secretion

  • eye

    • pupil dilation→ unresponsive to light

    • relaxation of ciliary muscle → fail to accomodate near vision

    • increase intraocular pressure

• Example

  • atropine and hyoscine

    • competitive antagonist

    • treat bradycardia

  • hyoscine

    • also competitive antagonist

    • facilitate endoscopy and GI radiology by relaxing the GI tract

    • antispasmodic agent in irritable bowel disease

  • tropicamide

    • eyedrops for ophthalmic examination

  • ipratropium

    • inhalation as brochodilator

  • Darifenacin

    • treat urinary incontinence due to overactive bladder