Histamine acts directly on calcitonin gene-related peptide- and substance P-containing trigeminal ganglion neurons as assessed by calcium influx and immunocytochemistry.

Primary cultures of rat trigeminal ganglion cells were exposed to histamine, and the intracellular free-calcium concentrations, [Ca2+]i, were measured by the calcium-sensitive dye fura-2. Histamine (10(-6)-10(-2) M) increased the [Ca2+]i of the neurons. Pretreatment of the cells with histamine H1-receptor blocker pyrilamine (10(-4) M), or chelation of extracellular calcium, abolished the response; however, the response was not altered by pretreatment with H2-blocker cimetidine (10(-2) M). Thus, the increase in [Ca2+]i was due to the influx of extracellular calcium mediated by H1-receptor. Immunocytochemical analysis showed that these cultured cells that respond to histamine were identically calcitonin gene-related peptide (CGRP)- or substance P (SP)-like immunoreactive. The findings suggested that histamine released from mast cells directly affected CGRP- and SP-containing sensory neurons via H1-receptor, which convey nociceptive information.