Chemical Transmission in Neurobiology

Study Notes

Acetylcholine (ACH)
- Found in all preganglionic neurons, all autonomic ganglia, and parasympathetic postganglionic neurons
- Also found in sympathetic postganglionic neurons to sweat glands and vasodilators of blood vessels in skeletal muscles, adrenal medulla, and the neuromuscular junction
- Synthesised from choline and active acetate using choline acetyl transferase
- Broken down by the enzyme choline esterase into acetic acid and choline
- Destroyed faster than noradrenaline

Present in granulated vesicles of nerve terminals in most sympathetic postganglionic endings and some brain neurons
Synthesised from tyrosine through a series of enzymatic steps:
- Tyrosine hydroxylase converts tyrosine to DOPA
- DOPA decarboxylase converts DOPA to dopamine
- Dopamine is converted to noradrenaline in granulated vesicles
Inactivated by:
- Active neuronal reuptake
- Monoamine oxidase (MAO) enzyme
- Catechol-O-methyl transferase (COMT) enzyme

Stimulated by acetylcholine
Classified into two types:
- Muscarinic Receptors
  - Stimulated by muscarine
- Nicotinic Receptors
  - Stimulated by nicotine

Muscarinic Actions (Parasympathetic)
- Cardiac inhibition and decrease in heart rate
- Pupillary constriction and accommodation
- Stimulation of salivary secretion
- Stimulation of gastrointestinal secretion and motility
- Contraction of the urinary bladder and rectum
- Bronchoconstriction
Nicotinic Actions
- Stimulation of autonomic ganglia
- Stimulation of the adrenal medulla to secrete adrenaline and noradrenaline
- Stimulation of the neuromuscular junction, causing skeletal muscle contraction

α Receptors
- On smooth muscle: mostly excitatory, causing contraction
- On blood vessels: vasoconstriction
- On sphincters: contraction of sphincters in the gastrointestinal tract, bladder, and rectum
β Receptors
- On smooth muscle: mostly inhibitory, causing relaxation
- On blood vessels: vasodilation
- On sphincters: relaxation of sphincters

Drugs that can increase or decrease the actions of the parasympathetic nervous system
Classified into two groups:
- Parasympathomimetic drugs
  - Induce effects similar to acetylcholine (or increase its actions)
  - Also called choline agonists
  - Include:
    - Drugs stimulating cholinergic receptors
      - Muscarinic agonists: e.g., muscarinic
      - Nicotinic agonists: e.g., nicotine in small doses
    - Drugs inhibiting the choline esterase enzyme
      - Reversible choline esterase inhibitors: temporary action, e.g., eserine and prostigmine.
      - Irreversible choline esterase inhibitors: permanent action, e.g., parathion
- Parasympatholytic drugs
  - Block the effects of acetylcholine (or decrease its actions)
  - Include:
    - Muscarinic blockers: e.g., atropine, used as pupil dilator, spasmolytic, and to decrease bronchial secretions
    - Nicotinic blockers: e.g., nicotine in large doses, used as ganglionic blockers, hexamethonium
    - Neuromuscular blockers: e.g., curare

Drugs that can increase or decrease the actions of the sympathetic nervous system
Classified into two groups:
- Sympathomimetic drugs
  - Induce effects similar to catecholamines (or increase its actions)
  - Include:
    - Drugs stimulating the ganglia: e.g., nicotine in small doses
    - Drugs increasing the release of NE from nerve endings: e.g., amphetamine
    - Drugs stimulating adrenergic receptors: e.g.,
      - α agonists: noradrenaline
      - β agonists: adrenaline
- Sympatholytic drugs
  - Block the effects of catecholamines (or decrease their actions)
  - Include:
    - Drugs blocking the ganglia: e.g., nicotine in large doses
    - Drugs decreasing the release of NE from nerve endings: e.g., reserpine
    - Drugs blocking adrenergic receptors: e.g.,
      - α blockers: phentolaimine
      - β blockers: propranolol