Adrenergic Transmission and Noradrenaline Release

Adrenergic Transmission

• Noradrenaline (NA) is synthesized in the axon of noradrenergic neurons.
• Tyrosine is converted to DOPA by tyrosine hydroxylase.
• DOPA is converted to dopamine by DOPA decarboxylase.
• Dopamine is converted to noradrenaline by dopamine hydroxylase.
• In the adrenal medulla, noradrenaline is converted to adrenaline by phenylethanolamine N-methyl transferase.

Storage and Release of Noradrenaline

• Noradrenaline is stored with ATP in synaptic vesicles.
• Noradrenaline is released via exocytosis when calcium ions enter the presynaptic neuron.
• Noradrenaline can also be released by non-exocytosis through the action of drugs like amphetamine.
• Auto-inhibitory feedback regulates noradrenaline release. Noradrenaline stimulates α2 receptors in the presynaptic neuron, inhibiting further release.

Elimination of Catecholamines

• Catecholamines (NA, adrenaline, isoprenaline) are eliminated by reuptake and metabolic degradation.
• Reuptake:
  • Uptake 1: Noradrenaline is taken up by the presynaptic neuron.
  • Uptake 2: Adrenaline is taken up by effector organs like the heart and smooth muscle.
• Metabolism:
  • Monoamine oxidase (MAO): degrades catecholamines in the mitochondria of cells.
  • Catechol-O-methyl transferase (COMT): found in neuronal and non-neuronal tissues, also degrades catecholamines.

Adrenoceptors

• Adrenoceptors are divided into two classes:
  • α receptors: α1 and α2
  • β Receptors: β1, β2, and β3

Action of Adrenergic Receptors

• α1 receptors:
  • Found in smooth muscle, causing vasoconstriction, GI relaxation, sphincter contraction, and mydriasis (dilation of pupils).
• α2 receptors:
  • Found in presynaptic neurons, the CNS, and blood vessels, inhibiting transmitter release and promoting platelet aggregation.
  • Postsynaptically, they can function similarly to α1 receptors.
• β1 receptors:
  • Found primarily in the heart, increasing contractility and heart rate.
• β2 receptors:
  • Found in smooth muscle, causing bronchodilation, peripheral vasodilation, visceral smooth muscle relaxation, skeletal muscle tremor, increased aqueous humor secretion, and increased liver glycogenolysis.
• β3 receptors:
  • Their exact functions are not fully understood.
• Adrenaline, noradrenaline, and isoprenaline act on both α and β receptors with varying potencies.
  • Noradrenaline preferentially stimulates α receptors, while isoprenaline preferentially stimulates β receptors.

Acetylcholine (ACh) Synthesis

• Choline, taken up from the extracellular fluid, enters the cytoplasm of cholinergic neurons via an energy-dependent carrier system.
• Choline acetyltransferase catalyzes the reaction of choline with acetyl coenzyme A (CoA) to form acetylcholine.

Acetylcholine (ACh) Storage

• Acetylcholine is actively transported into presynaptic vesicles.
• These mature vesicles contain acetylcholine, ATP, and proteoglycans.
• Vesamicol blocks the transport of acetylcholine into synaptic vesicles.

Acetylcholine (ACh) Release

• An action potential triggers the opening of voltage-gated calcium channels at the nerve terminal.
• Calcium influx promotes the fusion of vesicles with the cell membrane, releasing acetylcholine into the synaptic space.
• Botulinum toxin blocks the release of acetylcholine.

Acetylcholine (ACh) Degradation and Recycling

• Acetylcholinesterase rapidly cleaves acetylcholine into choline and acetate in the synaptic cleft, terminating the signal.
• Choline is recaptured by a high-affinity uptake system, transporting it back into the neuron for the synthesis of new acetylcholine.

Acetylcholine (ACh) Receptors:

• There are two major classes of acetylcholine receptors in the parasympathetic system:
  • Nicotinic receptors:
  • Muscarinic receptors: