Rapidly-adapting receptor activity and intratracheal pressure in guinea pigs. I. Action of leukotriene C4.
Leukotriene C4 (LTC4) is a major component of slow-reacting substance of anaphylaxis (SRS-A) and is a potent bronchoconstrictor. In humans LTC4 results in bouts of coughing which suggests stimulation of pulmonary receptors involved in a reflex mechanism. Furthermore, atropine reduces the effect of both LTC4 and SRS-A. To test the hypothesis that LTC4 stimulates the rapidly-adapting or "irritant" receptor (RAR) of the airways, we administered LTC4 by both intravenous injection (10-1000 ng) and by aerosol delivery (1 microgram/ml) to the lungs of guinea pigs while recording arterial blood pressure, intratracheal pressure, and nerve activity from RARs. LTC4 (i.v.) concurrently increased both nerve activity and intratracheal pressure even at low doses in a dose-dependent manner. Therefore, a direct action of LTC4 (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 LTC4. The pattern of RAR activity during LTC4 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.
D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D011312:Pressure; D011661:Pulmonary Stretch Receptors / Q000187:drug effects / Q000502:physiology*; D013189:SRS-A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D000336:Aerosols; D002867:Chromones; D013189:SRS-A; C006312:FPL 55712