Effect of age on the formation of cyclic nucleotides in guinea-pig tracheal smooth muscle in response to pharmacological agents.

The effects of isoproterenol, carbachol and other drugs on the cyclic AMP and cyclic GMP levels in tracheal smooth muscles of guinea-pigs of four different ages were investigated. Isoproterenol increased the cyclic AMP level several-fold in tracheal muscles from newborn (1 week) and young (4-7 weeks) guinea-pigs, but it caused less increase in the level in muscles from middle-aged (12 weeks) and old (20-24 weeks) guinea-pigs, although the basal cyclic AMP level at these ages was not significantly lower. The effects of prostaglandin E1 and cholera toxin in increasing the cyclic AMP level were also markedly less in muscle preparations from old guinea-pigs than in those from young ones. The increase in cyclic AMP levels caused by forskolin, an activator of adenylate cyclase did not decrease with age. Carbachol caused a 3- to 4-fold increase in the cyclic GMP level in muscle preparations from newborn and young guinea-pigs and more increase in the cyclic GMP level in preparations from middle-aged and old guinea-pigs. The increases in cyclic GMP level induced by high K+, histamine and sodium nitroprusside also increased with the age of the animals. These results suggest that the changes in the formation of cyclic AMP and cyclic GMP induced by various agents are due to changes at the post-receptor level.