CARBACHOL, NOREPINEPHRINE, AND HYPOCAPNIA STIMULATE PHOSPHATIDYLINOSITOL TURNOVER IN RAT TRACHEAL SLICES

Background: The intracellular mechanisms involved in the alpha-adrenoc eptor- or hyperventilation-induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol ( PI) metabolism and airway smooth muscle contraction induced by muscari nic agonists, the authors examined the effects of carbachol (CCh), nor epinephrine (NE), and hypocapnia on PI turnover in the airway smooth m uscle. Methods: Rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [H-3]myo-inositol in the presence of NE, CCh, or neither, The P-CO2 in the solution was 36 +/- 3 mmHg (normocap nia), 19 +/- 2 mmHg (moderate hypocapnia), or 5 +/- 2 mmHg (severe hyp ocapnia), respectively, [H-3]inositol monophosphate (IP1) formed was c ounted with a liquid scintillation counter. Results: Basal IP1 formed was greater at severe hypocapnia than at normocapnia, Norepinephrine- and CCh-induced IP1 formation were also greater at hypocapnia than at normocapnia. Conclusions: These results indicate that CCh, NE, and hyp ocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE- and CCh-i nduced PI turnover, which could cause worsening of exercise-induced as thma and vagotonic asthma, respectively.