2.4 Neurotransmitters

Neurotransmitters

Chemicals released at chemical synapses that bind to the postsynaptic cell.

Requirements for neurotransmitters

Must be synthesized within presynaptic neuron, released by presynaptic neuron, cause the same effect when applied to postsynaptic neuron, and have mechanisms for inactivation or clearance.

Small molecule neurotransmitters

Synthesized and stored in the terminal for fast release.

Peptide neurotransmitters

Synthesized in the cell body and transported to the terminal, leading to slower release.

Amino acid neurotransmitters

A group of small molecule neurotransmitters.

Biogenic amines

Also called monoamines, a group of small molecule neurotransmitters.

Glutamate

The main excitatory neurotransmitter used by the nervous system.

AMPA and kainate

Receptors that allow both sodium and potassium to cross the membrane.

NMDA

Requires binding of glutamate to open and is also dependent on voltage.

Glutamine

Converted into glutamate via the enzyme glutaminase.

Vesicular glutamate transporter (vGLUT)

Packages glutamate into small vesicles for storage.

GABA

Gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain.

Glycine

Another inhibitory neurotransmitter mainly used in the spinal cord and brainstem.

Serine hydroxy methyltransferase

Converts amino acid serine into glycine in the presynaptic terminal.

Glutamic acid decarboxylase (GAD)

Converts glutamate into GABA in the presynaptic terminal.

Vesicular inhibitory amino acid transporter (VIAAT)

Packages GABA into small vesicles for storage.

Dopamine

A biogenic amine derived from tyrosine, known for its role in reward and movement.

Tyrosine

Converted into DOPA via tyrosine hydroxylase, the rate limiting step in synthesis of catecholamines.

Vesicular monoamine transporter (VMAT)

Packages dopamine into small synaptic vesicles.

Acetylcholine

Best known for its role at the neuromuscular junction.

Acetyl coenzyme A (acetyl CoA)

Synthesis of acetylcholine occurs from acetyl CoA and choline via choline acetyltransferase (ChAT).

Vesicular acetylcholine transporter (VAChT)

Packages acetylcholine into small vesicles for storage.

Norepinephrine

Cells producing norepinephrine are localized in the locus coeruleus in the pons.

Epinephrine

Triggers 'fight or flight' response, released by adrenal medulla.

Dopamine beta-hydroxylase

Converts dopamine into norepinephrine.

Nicotinic acetylcholine receptors

Ionotropic receptors activated by nicotine and acetylcholine.

Muscarinic acetylcholine receptors

GPCRs that utilize an indirect mechanism of action.

D1-like receptors

Typically associated with Gαs, activating the cAMP/adenylyl cyclase system.

D2-like receptors

Typically associated with Gαi, inhibiting the cAMP/adenylyl cyclase system.

Neuropeptides

Class of large signal molecules synthesized by some neurons.

Endocannabinoids

Endogenous lipid-based neurotransmitters that signal in a retrograde manner.

Nitric Oxide

Gas transmitter synthesized as needed from arginine.

Soluble guanylate cyclase (sGC)

Linked with cyclic GMP (cGMP) which activates protein kinase G (PKG).

Small vesicles

Diameter of 40 nm, store most traditional neurotransmitters.

Large dense-core vesicles

Diameter of 100-250 nm, store neuropeptides.

Vesicular ATP-ase

Maintains high concentration of H+ ions in vesicles.

Neurotransmitter Inactivation

Includes diffusion, enzymatic degradation, and reuptake.

Two major categories of neurotransmitters

Small molecule neurotransmitters and peptide neurotransmitters

Two classes of dopamine metabotropic receptors on postsynaptic cells

D1-like receptors and D2-like receptors

Name all atypical neurotransmitters (all endogenous=created by the body)

Neuropeptides, Endocannabinoids, Nitric Oxide and sGC

Name the two types of vesicles

Small and large synaptic vesicles