Modulation of fluoroaluminate-induced inositol phosphate formation by increases in tissue cyclic AMP content in bovine tracheal smooth muscle.
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.
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
I P
IP
Hall
J
J
Donaldson
S J
SJ
Hill
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000535:Aluminum / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D005461:Fluorine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D007295:Inositol Phosphates; C053629:fluoroaluminum; D005461:Fluorine; D012969:Sodium Fluoride; D000535:Aluminum; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D007545:Isoproterenol; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine