Table 1.
Pruritogens and mechanisms
| category | pruritogen | Scratching | itch humans | mechanisms | ||
|---|---|---|---|---|---|---|
| CD-1 mice | C57BL/6 mice | SD rats | ||||
| amines | histamine | + | + | − | + | H1/H4 receptor, PLC-β3, TRPV1 |
| 5-HT | + | + | + | + | 5-HT2 receptor | |
|
| ||||||
| proteases (tethered ligands) | SLIGRL | + | + | − | + | PAR-2, MrgprC11 |
| AYPGKF | + | + | − | N.T. | PAR-4 | |
| tryptase | + | N.T. | N.T. | N.T. | PAR-2 | |
| mucunain | + | N.T. | N.T. | + | PAR-2, PAR-4 | |
| cathepsin S | N.T. | N.T. | N.T. | + | PAR-2, PAR-4, MgprC11 | |
|
| ||||||
| neuropeptides | substance P | + | N.T. | − | + | mast cell degranulation, NK1 receptor, LTB4, NO |
| endothelin-1 | + | + | + | + | ETA receptor | |
|
| ||||||
| lipid mediators | PAF | N.T. | N.T. | + | + | PAF receptor |
| LPA | + | N.T. | N.T. | N.T. | histamine, Rho-ROCK | |
| LTB4 | + | N.T. | N.T. | N.T. | BLT1 receptor | |
| TXA2 | + | N.T. | N.T. | N.T. | TP receptor | |
| SPC | + | N.T. | N.T. | N.T. | Rho-ROCK, LTB4 | |
| 12-HETE | + | N.T. | N.T. | N.T. | BLT2 receptor | |
|
| ||||||
| cytokines | IL-2 | N.T. | N.T. | N.T. | + | mast cell degranulation? |
| IL-31 | N.T. | + | N.T. | N.T. | IL31RA/OSMR | |
|
| ||||||
| Mrgpr agonists | chloroquine | + | + | − | +* | MrgprA3, TRPA1, mast cell degranulation |
| BAM8-22 | N.T. | + | N.T. | + | MrgprC11, TRPA1 | |
| β-alanine | N.T. | + | N.T. | + | MrgprD | |
|
| ||||||
| uncategorized | compound 48/80 | + | + | − | + | mast cell degranulation |
| Bile acids | N.T. | + | N.T. | + | TGR5 | |
| oxidative stress | N.T. | + | N.T. | N.T. | TRPA1 | |
| TLR7 agonists | N.T. | + | N.T. | N.T. | TLR7, K2P, Kv1.1, Kv1.2 | |
+, induction of itch or scratching; −, no induction of itch or scratching; N.T., not tested;
oral administration
Abbreviations: 5-HT, 5-hydroxytryptamine (serotonin); PAF, platelet activating factor; LPA, lysophosphatidic acid, LTB4, leukotriene B4; TXA2, thromboxane A2; SPC, sphingosylphosphorylcholine; 12-HETE, 12-Hydroxyeicosatetraenoic acid; BAM8-22, bovine adrenal medullary peptide 8-22; TLR7, toll-like receptor 7; H, histamine; PAR, protease-activated receptor; NO, nitric oxide; ETA, endothelin-1 A, Rho-ROCK, Rho-associated protein kinase; BLT, LTB4 receptor; IL31, interleukin 31; OSMR, oncostatin M receptor; Mrgpr, Mas-related G-protein-coupled receptor; TP, thromboxane receptor; TGR5, G protein-coupled bile acid receptor 1 (GPBAR1); TRPA1, transient receptor potential ankyrin 1; K2P, two-pore-domain potassium channels; Kv, voltage-gated potassium channel.