2 Neuroscience2.5 Neurochemistry and neurophysiology
2.5.2.3 Receptor structure and function; presynaptic and postsynaptic receptors
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Written by Resident Doctor Committee · Published
Receptor classes
Class | Structure | Signalling | Examples |
|---|---|---|---|
Ionotropic | Ligand-gated channel whose own subunits form the pore | Fast, direct change in conductance | GABA-A, nicotinic, NMDA, 5-HT3 |
Metabotropic | G protein-coupled receptor with seven transmembrane segments | Indirect, through second messengers | All dopamine receptors, GABA-B, muscarinic |
Nuclear | Intracellular | Enters the nucleus after steroid binds, then regulates gene transcription | Glucocorticoid receptor |
Metabotropic effects are slower to start, longer lasting and more widespread than ionotropic ones.
Cys-loop channels (GABA-A, nicotinic, glycine, 5-HT3) are pentamers: five subunits form a rosette around a central pore.
Ionotropic glutamate receptors (NMDA, AMPA and kainate) are tetramers.
Receptors by transmitter
Transmitter | Ionotropic | Metabotropic coupling |
|---|---|---|
Noradrenaline | None | Alpha-1 Gq; alpha-2 Gi/o; beta Gs |
Serotonin | 5-HT3 only | 5-HT1 Gi/o; 5-HT2 Gq |
Dopamine | None | D1 and D5 Gs or Golf; D2, D3 and D4 Gi/o |
GABA (gamma-aminobutyric acid) | GABA-A | GABA-B Gi/o |
Acetylcholine | Nicotinic | M1, M3 and M5 Gq; M2 and M4 Gi/o |
Glutamate | AMPA, NMDA (N-methyl-D-aspartate), kainate | Group I mainly Gq; groups II and III mainly Gi/o |
Dopamine has no ionotropic receptor; D1 is the most abundant and widespread subtype in brain, with D2 second.
5-HT3 is a cation channel on vagal afferents and in the area postrema; ondansetron blocks it to prevent chemotherapy-induced vomiting.
mGlu5 is a metabotropic glutamate receptor that raises intracellular calcium through inositol trisphosphate.
NMDA receptor
Calcium enters only when three conditions are met:
Glutamate binds GluN2.
A co-agonist binds GluN1: glycine, or D-serine at many forebrain synapses.
Depolarisation clears magnesium from the channel.
Endogenous ligands
Receptor | Endogenous ligand | Points to know |
|---|---|---|
Kappa-opioid | Dynorphin | Activation causes dysphoria and reduces dopamine release; salvinorin A acts here |
CB1 and CB2 | 2-Arachidonoylglycerol | Full agonist of high efficacy; more abundant in brain than anandamide |
CB1 and CB2 | Anandamide | Partial agonist of low efficacy |
CB2 is the immune and microglial cannabinoid receptor.
Presynaptic and postsynaptic receptors
Autoreceptors detect the cell's own transmitter and usually restrain its firing or release.
Heteroreceptors detect other transmitters.
Blocking alpha-2 receptors can increase noradrenergic and serotonergic signalling.
Adaptation of somatodendritic 5-HT1A autoreceptors is one proposed part of the response to selective serotonin reuptake inhibitors.
Extrasynaptic GABA-A receptors produce tonic inhibition.