Phospholipase Cβ3 mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons

Phospholipase C beta (PLC beta) isozymes represent a family of molecules that link G protein-coupled receptors (GPCRs) to an intracellular signaling network. Here, we investigated the function of PLC beta isozymes in sensory neurons by using mutant mice deficient for specific PLC beta family members. Expression analysis indicated that PLC beta 3, one of the four isoforms, is predominantly expressed in a subpopulation of C-fiber nociceptors. A subset of these neurons expressed the histamine H1 receptor. Ca2+ imaging studies revealed that PLC beta 3 specifically mediates histamineinduced calcium responses through the histamine H1 receptor in cultured sensory neurons. In line with this, we found that PLC beta 3(-/-) mice showed significant defects in scratching behavior induced by histamine; histamine-trifluoromethyl-toluidine(HTMT), a selective H1 agonist; and compound 48/80, a mast cell activator. These results demonstrate that PLC beta 3 is required to mediate "itch" sensation in response to histamine acting on the histamine H1 receptor in C-fiber nociceptive neurons.