Carbachol, norepinephrine, and hypocapnia stimulate phosphatidylinositol turnover in rat tracheal slices.
BACKGROUND
The intracellular mechanisms involved in the alpha-adrenoceptor- or hyperventilation-induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle.


METHODS
Rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [3H]myo-inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 +/- 3 mmHg (normocapnia), 19 +/- 2 mmHg (moderate hypocapnia), or 5 +/- 2 mmHg (severe hypocapnia), respectively. [3H]inositol monophosphate (IP1) formed was counted 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 hypocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE- and CCh-induced PI turnover, which could cause worsening of exercise-induced asthma and vagotonic asthma, respectively.
Shibata
O
O
Department of Anesthesiology, Nagasaki University School of Medicine, Japan.
Makita
T
T
Tsujita
T
T
Tomiyasu
S
S
Fujigaki
T
T
Nakamura
H
H
Sumikawa
K
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D016857:Hypocapnia / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D002217:Carbachol; D009638:Norepinephrine