Table I.
GPCR alterations identified in animal models, ex vivo assays and patients with SZ.
| GPCR | Associated signaling | Implications in SZ | (Refs.) |
|---|---|---|---|
| Type D1 (D1 and D5) | Gαq/Gs | Elevated mRNA levels of D1 receptors in the temporal and parietal cortex | (93) |
| Type D2 (D2-4) | Gαi/Go | Overexpression in the striatum leads to deficits in inhibitory neurotransmission and dopamine sensitivity in the prefrontal cortex | (92) |
| Adrenergic (α1, β1-3) Adrenergic (α2, β2, β3) |
Gαq/Gs Gαi |
Positive symptoms are exacerbated by selective and indirect norepinephrine receptor agonists, while antagonists decrease symptoms | (295) |
| Muscarinic (M1, M3, M5) Muscarinic (M2, M4) |
Gαq/G11 Gαi/Go |
Transcriptional and proteomic alterations in M1 and M4 receptors in the hippocampus and prefrontal, frontal and cingulate cortex | (296,297) |
| mGlu (mGluR1, mGluR5) | Gαq/Gs | Overexpression of mGluR1 in the prefrontal cortex of patients | (152) |
| mGlu (mGluR2-4 and 6-8) | Gαi/Go | mGluR2/3 may serve a role in working memory associated with NMDA receptor hypofunction | (82,298) |
| Serotonergic (5-HT1, 5-HT5) | Gαi/Go | Decreased binding of 5HT to the 5-HT1A receptor in the amygdala of patients | (299) |
| Serotonergic (5-HT2) | Gαq | Alterations in frontal cortical 5-HT2A receptor binding and decreased receptor density in the brain of patients | (300) |
| Serotonergic (5-HT4, 5-HT6, 5-HT7) | Gαs | 5-HT7 in the human brain and reduced mRNA levels in the prefrontal cortex of patients | (301) |
| GABAB metabotropic (GBR2) | Gαi/Gβγ | GABABR1 (6p21.3) and GABABR2 (5q34) gene loci are SZ susceptibility loci | (302) |
GPCR, G protein-coupled receptor; SZ, schizophrenia; D, dopamine; mGluR, glutamate metabotropic receptor; NMDA, N-methyl-d-aspartate; 5-HT, serotonin; GBR, GABA metabotropic receptor.