Mepyramine but not cimetidine or clobenpropit blocks pertussis toxin-induced histamine sensitization in rats

1 The effects of pertussis toxin (PT) and the role of histaminergic H-1, H- 2 and H-3 receptor blockade on the actions of histamine on blood pressure, heart rate, blood gas values, and mortality were studied in anaesthetized r ats. 2 Four days after treatment with PT, histamine dose-dependently decreased m ean arterial blood pressure (MAP) and PT enhanced the histamine-induced dec rease in MAP. In the PT but not in the inactivated PT (IPT) or saline treat ed group three out of six animals died after the highest dose of histamine (300 mg kg(-1), i.v.) 3 In order to determine the type of histamine receptor that mediates HS, 4 days after PT the selective antagonists mepyramine (H-1), cimetidine (H-2) and clobenpropit (H-3) were administered 20 min before the challenge with h istamine. Mepyramine completely inhibited both the enhanced histamine-induc ed decrease in MAP and mortality brought about by PT. Cimetidine and cloben propit had no protective effects, but rather enhanced the histamine-induced mortality elicited by PT. 4 The present study shows that PT caused HS in rats which is primarily medi ated via H-1 and secondarily via H-2 and H-3 receptors. These results are c onsidered to be a first step in the elucidation of the mechanism(s) of the HS test used in the quality control of acellular pertussis vaccine.