MrgprD is required for β-alanine-induced scratching in mice. A, Cheek injection of β-alanine induced site-directed scratching in WT but not MrgprD−/− mice. β-alanine induced significant scratching in WT mice during the first 15 min after injection in a dose-dependent manner (50 mm, n = 6; 20 mm, n = 5; 10 mm, n = 5). In contrast, few scratching bouts were detected in MrgprD−/− mice after β-alanine cheek injection (n = 5). l-alanine, the proteinogenic α-amino acid, did not induce a significant itch response (WT, n = 6; KO, n = 8). B, Orally administering β-alanine induced itch in WT but not MrgprD−/− (KO) mice. The total number of scratching bouts during the 40 min after β-alanine feeding (40 mg/kg body weight) was significantly higher in WT mice than in MrgprD−/− mice (n = 5 per genotype; *WT vs KO). All error bars represent SEM. *p < 0.05, **p < 0.01; Student's t test.