Modulation of fluoroaluminate-induced inositol phosphate formation by increases in tissue cyclic AMP content in bovine tracheal smooth muscle

Br J Pharmacol. 1990 Jul;100(3):646-50. doi: 10.1111/j.1476-5381.1990.tb15861.x.

Abstract

1. The effect of fluoroaluminate complexes (AlCl3 plus NaF) upon smooth muscle tone, [3H]-inositol phosphate accumulation and [3H]-cyclic AMP accumulation has been investigated in slices of bovine tracheal smooth muscle. 2. Fluoroaluminate (10 microM AlCl3 + various concentrations of NaF) elicited concentration-dependent contractions of bovine tracheal smooth muscle strips at concentrations of NaF in the range 1-10 mM. The resultant contractile response was reversed by isoprenaline (50 nM) and was preserved in calcium-free medium. 3. Fluoroaluminate stimulated [3H]-inositol phosphate formation at concentrations of NaF over 1 mM. The response to 20 mM NaF + 10 microM AlCl3 was 164 +/- 29% of the response to 1 mM histamine. Fluoroaluminate also increased the incorporation of [3H]-myo-inositol into membrane phospholipids. 4. Fluoroaluminate produced a small rise in [3H]-cyclic AMP levels (2.1 fold increase over basal with 20 mM NaF). The response to forskolin (1 microM, 8.6 fold over basal) was reduced by fluoroaluminate in a concentration-dependent manner, but still remained significantly (P less than 0.05) elevated over the response to fluoroaluminate alone. 5. The [3H]-inositol phosphate response to fluoroaluminate was inhibited by salbutamol (maximum inhibition 60%, IC50 = 0.08 microM), forskolin (1 microM, 46% inhibition) and isobutylmethylxanthine (1 mM, 73% inhibition). 6. These data suggest that inhibition of agonist-induced inositol phospholipid turnover by cyclic AMP in this tissue can occur at the post-receptor level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Albuterol / pharmacology
  • Aluminum / antagonists & inhibitors
  • Aluminum / pharmacology*
  • Animals
  • Cattle
  • Cyclic AMP / metabolism*
  • Fluorine / antagonists & inhibitors
  • Fluorine / pharmacology*
  • In Vitro Techniques
  • Inositol Phosphates / metabolism*
  • Isoproterenol / pharmacology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Phosphoric Diester Hydrolases / metabolism
  • Sodium Fluoride / pharmacology
  • Trachea / drug effects
  • Trachea / metabolism

Substances

  • Inositol Phosphates
  • fluoroaluminum
  • Fluorine
  • Sodium Fluoride
  • Aluminum
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • glycerophosphoinositol glycerophosphodiesterase
  • Isoproterenol
  • Albuterol
  • 1-Methyl-3-isobutylxanthine