Rapidly-adapting receptor activity and intratracheal pressure in guinea pigs I. Action of leukotriene C 4

Abstract

Leukotriene C 4 (LTC 4) is a major component of slow-reacting substance of anaphylaxis (SRS-A) and is a potent bronchoconstrictor. In humans LTC 4 results in bouts of coughing which suggests stimulation of pulmonary receptors involved in a reflex mechanism. Furthermore, atropine reduces the effect of both LTC 4 and SRS-A. To test the hypothesis that LTC 4 stimulates the rapidly-adapting or “irritant” receptor (RAR) of the airways, we administered LTC 4 by both intravenous injection (10–1000 ng) and by aerosol delivery ( 1 ug/ml) to the lungs of guinea pigs while recording arterial blood pressure, intratracheal pressure, and nerve activity from RARs. LTC 4 (i.v.) concurrently increased both nerve activity and intratracheal pressure even at low doses in a dosedependent manner. Therefore, a direct action of LTC 4 (i.v.) upon the RAR is difficult to conclude. The separation of peak tracheal pressure and peak nerve activity was apparent with aerosol delivery of LTC 4. The pattern of RAR activity during LTC 4 aerosol challenge was unrelated to respiratory phase. FPL 55712 blocks the effects of SRS-A. We challenged the lung with 500 ng LTC4 intravenously before and after FPL 55712 injection (2.5 mg/kg). FPL 55712 blocked the increases of both tracheal pressure and RAR activity.