Neurotransmitters: Types, Fibers, Receptors, and Termination

Overview: Chemical Classes of Neurotransmitters

• Amino-acid neurotransmitters

  • Pure, unmodified amino acids that double as protein–building residues.
  • Principal examples: GABA, glutamate, aspartate.
  • Function directly “as-is”; no additional chemical groups are required for activity.

• Amine-based neurotransmitters (a.k.a. biogenic amines)

  • Derived from amino acids but are not exclusively the parent amino acid.
  • Built by adding or modifying functional groups on the amino-acid backbone.
  • Two important sub-groups:
  • Indolamine: Serotonin (5-HT)
    • Originates from tryptophan; extra chemical modifications provide biological activity.
  • Catecholamines: Dopamine, norepinephrine, epinephrine
    • All begin with tyrosine, then share the catechol ring + amine tail; diverge through sequential enzymatic steps.

• Purine neurotransmitters

  • ATP (adenosine triphosphate) & AMP (adenosine monophosphate) can be released by neurons.
  • Real-world callback: ATP acted as a paracrine signal in the pancreatic β-cell (previous lecture).

• Gaseous neurotransmitters

  • Nitric oxide (NO) and carbon monoxide (CO) diffuse directly across membranes.
  • CO reminder: lethal at high systemic concentrations due to competitive binding to hemoglobin.

• Lipid-derived transmitters (mentioned briefly)

  • Fatty molecules that can be enzymatically cleaved to yield signaling ligands.

• Two “special” categorical labels

  • Catecholamines (already listed) are grouped by shared catechol ring.
  • Acetylcholine (ACh) often stands alone as a unique class because of its historical & physiological importance.

Catecholamines & Acetylcholine: Detailed Focus

• Dopamine, norepinephrine (NE), epinephrine (EPI) = catecholamines.
• Epinephrine vs. norepinephrine nomenclature
  • UK term “adrenaline” ⇒ root for "adrenergic" (adrenergic fiber, receptor).
  • Functional difference: EPI usually circulates as a hormone; NE primarily serves as a neurotransmitter at synapses.
• Acetylcholine is synthesized from choline + acetyl-CoA.
  • Heavily utilized at neuromuscular junctions, autonomic ganglia, and multiple CNS circuits.

Cholinergic vs. Adrenergic Systems

• Fiber = axon (terminology: nerves are bundles of axons ➔ “fibers”).

Cholinergic Fiber

• Releases ACh.
• Illustrated example: vagal (parasympathetic) axon to the heart.

Cholinergic Receptors

• Bind ACh only ➔ therefore called cholinergic.
• Two structural subclasses:
  • Nicotinic (nAChR): classic ligand-gated ion channels (fast EPSP).
  • Muscarinic (mAChR): G-protein-coupled receptors (GPCRs) (slower, modulatory effects).
• Physiological note: ACh binding to cardiac muscarinic receptors ↓ heart rate (negative chronotropy).

Adrenergic Fiber

• Releases NE (± small EPI).
• Binds downstream adrenergic receptors on target tissue.

Adrenergic Receptors

• All are GPCRs.
• Two broad families with subtypes:
  • α (alpha)
  • β (beta)
• Cardiac effect: NE/EPI binding → ↑ heart rate & ↑ ventricular contraction force (positive chronotropy & inotropy).

Circuit Illustration: Mixed Neurochemical Chain

• Example shown: three neurons in series.
  1. Upstream neuron: releases ACh ⇒ cholinergic fiber.
  • Receptors on its dendrites unknown (not enough info).
  1. Middle neuron: receives ACh on dendritic cholinergic receptors, yet releases NE ⇒ adrenergic fiber.
  • Demonstrates that transmitter released ≠ transmitter detected on its own dendrites.
  1. Downstream neuron: receives NE on dendritic adrenergic receptors and itself releases NE ⇒ also adrenergic fiber.
• Key takeaway: classification of a neuron’s axon (its “fiber”) is independent of receptor complement on its soma/dendrites.

Termination of Neurotransmitter Action

• Continuous receptor activation would blur on/off signaling; hence each transmitter needs an off switch.

Passive Dissociation

• Some ligands simply detach after transient binding because affinity is time-limited.

Enzymatic Degradation & Re-uptake

• Acetylcholinesterase (AChE)
  • Hydrolyzes ACh → choline + acetyl-CoA.
  • Choline is recovered via a Na⁺–choline symporter (secondary active transport) and reused for ACh synthesis.

Clinical Pharmacology Example – SSRIs

• Selective Serotonin Re-uptake Inhibitors (e.g., Prozac, Paxil, Zoloft).
  • Block the transporter/enzyme complex that returns serotonin to the presynaptic neuron.
  • Prolongs 5-HT residence in the synaptic cleft ⇒ amplifies mood-stabilizing signaling.
  • Modern naming sometimes drops one "S" → “SRI.”

Connections, Implications, & Reminders

• Purine signaling (ATP) previously observed in endocrine (β-cell) communication; same molecule can be bona fide neurotransmitter.
• Toxicological angle: CO’s neurotransmitter role is concentration-dependent; high levels hijack hemoglobin.
• Receptor taxonomy: knowing whether a receptor is ionotropic (nicotinic) vs. metabotropic (muscarinic, all adrenergic subtypes) guides predictions about speed and second-messenger pathways.
• Upcoming content teaser: deeper dive into GPCR mechanics & ligand-gated ion channels in next lecture.