Autoregulation of histamine release via the histamine H3 receptor on mast cells in the rat skin.

The autoregulation of the histamine release via the histamine H3 receptor in the periphery was studied in vivo and in vitro. Antidromic electrical stimulation of the sciatic nerve caused a significant increase in histamine release in the subcutaneous perfusate in the rat hindpaw. (R)alpha-methylhistamine, a specific H3 receptor agonist, significantly and dose-dependently inhibited the increase in release of histamine by antidromic stimulation at intravenous doses of 0.25-2 mg/kg. Thioperamide (2 mg/kg, intraperitoneally), a specific H3 antagonist, prevented the inhibitory effect of (R)alpha-methylhistamine. Substance P perfusion (5-50 microM) also elicited a significant increase in histamine, and a significant inhibition by (R)alpha-methylhistamine and the antagonism of thioperamide were observed. (R)alpha-methylhistamine inhibited the histamine release by substance P from rat peritoneal mast cells in vitro, and thioperamide reduced the response to (R)alpha-methylhistamine. These data suggest that mast cells may have histamine H3 receptors, and that histamine probably modulates its own release through the H3 receptor in neurogenic inflammation.