Effects of age on muscarinic agonist-induced contraction and IP accumulation in airway smooth muscle.

The effects of age on carbachol-stimulated force development and [3H]inositol phosphate production was studied in tracheal rings from guinea pigs aged 1 month and 25 months of age. The pD2 for the contractile response to carbachol was significantly reduced in tracheal tissues from old animals as compared to that of the young tissues (6.49 +/- 0.04, 7.09 +/- 0.04, n = 12), respectively. In contrast, inositol phosphate formation was not altered with increasing age when stimulated by carbachol or NaF, a direct activator of G proteins. Carbachol-induced inositol phosphate accumulation was inhibited by treatment with 1 micrograms/ml pertussis toxin, suggesting that IP1 accumulation is coupled to a pertussis-toxin-sensitive protein. The pD2 values for contraction (7.09 +/- 0.09, 6.49 +/- 0.04) were significantly different from the pD2 values for IP1 accumulation (4.72 +/- 0.14, 5.10 +/- 0.18) in both young and old tissues, respectively. These data suggest that IP1 accumulation is not responsible for the decreased contractile ability in tracheal smooth muscle during aging.