3 Clinical psychopharmacology3.3 Pharmacodynamics
3.3.1.2.1 Metabotropic and G protein coupled receptors
1 min read1 figure
Written by Resident Doctor Committee · Published
Metabotropic versus ionotropic receptors
Metabotropic receptors are G protein-coupled receptors (GPCRs) with no intrinsic ion channel. They signal through intracellular intermediaries that regulate separate channels, enzymes and gene expression.
Ionotropic receptors are ligand-gated ion channels that conduct ions directly when the transmitter binds.
Glutamate, gamma-aminobutyric acid (GABA) and acetylcholine have both kinds: ionotropic receptors mediate fast transmission, and metabotropic receptors modulate it.
Structure
A GPCR crosses the membrane seven times as alpha helices, with an extracellular N terminus and an intracellular C terminus.
The intracellular face of the receptor engages G proteins, which carry the signal on.
Which receptors are GPCRs
Dopamine, adrenergic, muscarinic, histamine, opioid and cannabinoid receptors are GPCRs, as are GABA B and metabotropic glutamate receptors.
All serotonin (5-HT) receptors are GPCRs except 5-HT3, which is ionotropic.
CB1 and CB2, the endocannabinoid receptors, are GPCRs, not ligand-gated ion channels. CB1 is concentrated presynaptically in the brain, and CB2 is mainly immune and peripheral.
Drugs of misuse
Drug | Receptor it acts at first | Receptor type |
|---|---|---|
Heroin, through morphine and 6-monoacetylmorphine | Mu-opioid | GPCR |
Cannabis, through tetrahydrocannabinol | CB1 | GPCR |
Lysergic acid diethylamide (LSD) | 5-HT2A | GPCR |
Mu-opioid and CB1 receptors couple to Gi/o, which inhibits adenylyl cyclase so cyclic AMP falls.
Most other drugs of misuse act first at ligand-gated ion channels or at non-receptor targets.