Functional Role of Cyclic Nucleotides

Abstract

Delineation of specific roles of cyclic nucleotides, in particular cyclic AMP, in the nervous system has been based primarily on attempts to correlate alterations of cyclic AMP and/or cyclic GMP levels in intact cells, tissues, or organs with alterations in (1) metabolic pathways, (2) cell differentiation, and growth and expression of the phenotype, (3) membrane function, and (4) central behavioral and vegetative effects. Enhanced intracellular levels of cyclic AMP or a functionally “equivalent” analog have been expected to pertain as a result of the following: (1) the presence of high concentrations of extracellular cyclic AMP, dibutyryl cyclic AMP, butyryl cyclic AMP, 8-benzylthio cyclic AMP, etc.; (2) the presence of a phosphodiesterase inhibitor such as theophylline, isobutylmethylxanthine, papaverine, or RO 20–1724; and/or (3) the presence of an agent that is a stimulant of cyclic AMP-generating systems in neuronal or glial cells i.e., biogenic amines, adenosine, prostaglandin, or depolarizing agents. Antagonists of the stimulatory agents have also been employed to advantage. Similar paradigms have been employed to alter cyclic GMP levels, for example, through the use of dibutyryl cyclic GMP* or agents such as acetylcholine that stimulate cyclic GMP-generating systems. The difficulties in establishing such correlations are apparent.