Guanosine 3':5'-cyclic monophosphate and the action of insulin and acetylcholine.

Low concentrations of insulin (120 muunits/ml) and of carbamylcholine (1 muM) increase cyclic GMP content in isolated fat cells by 350%. The maximal amount of cyclic GMP, achieved within 2 min after addition of insulin or carbamylcholine, falls rapidly for insulin and much more slowly for carbamylcholine. 10 pM Acetylcholine can also augment the content of fat-cell cyclic GMP, but by 5 min (37 degrees ) the amount falls to that of unstimulated cells. Atropine abolishes the effects of carbamylcholine and acetylcholine but does not modify that of insulin, indicating that the ability of insulin to regulate cyclic GMP levels is not mediated by cholinergic receptors. Insulin and carbamylcholine increase the concentration of cyclic GMP in rat-liver slices by 400%; the effects of both agents occur rapidly and are relatively transient. Insulin does not alter cyclic GMP concentrations in purified human peripheral lymphocytes or in rat-spleen lymphocytes, cells which possess few insulin receptors and which are insensitive to the metabolic effects of the hormone. Carbamylcholine, however, causes a substantial increase in the cyclic GMP content of these lymphocytes. The data support the view that close and reciprocal relationships may exist between the concentrations and actions of cyclic AMP and cyclic GMP, as well as between the enzymes responsible for biosynthesis and degradation of these nucleotides.