Effects of adrenergic and cholinergic stimulations on cyclic nucleotides metabolism in bone of young rat.

Epinephrine or carbachol, alone or together with parathyroid hormone (PTH) or calcitonin, was added into the incubation of young rat tibia and cyclic AMP as well as cyclic GMP in the tissue was determined. Epinephrine induced a dose related and rapid increase of cyclic AMP probably through mechanism different from that of PTH or calcitonin. The effect of these hormones to increase cyclic AMP was additive to the effect of maximal dose of epinephrine and, in contrary to epinephrine effect, was not influenced by propranolol. Carbachol induced a dose-related and rapid increase of cyclic GMP in bone. The effect of carbachol was completely abolished by adding atropine or tetracaine. A marked increase of cyclic GMP was also induced by NaN3. There was no reciprocal relationship between the levels of cyclic AMP and cyclic GMP. The increase of cyclic GMP by carbachol was unaffected by the increase of cyclic AMP induced by PTH, and the increase of cyclic AMP by PTH or calcitonin was the same in the presence or absence of carbachol at the dose maximally effective to increase cyclic GMP. The results indicate the presence in bone of adrenergic and cholinergic receptor sites, and possible regulation of bone cell activity by these nervous systems through cyclic AMP and cyclic GMP. Though the regulation of the cyclic nucleotides content in bone by these neurotransmitters appeared to be through mechanism independent of PTH or calcitonin action, it seems worth-while to study further how these neurotransmitters by themselves or in concert with these hormones act on the various aspects of bone cell function.