Exogenous Dibutyryl Cyclic AMP Research Articles

Intracellular Cyclic Adenosine 3’, 5’-Monophosphate and Relaxing Effects of Isoprenaline and Papaverine on Smooth Muscle of Intestine

The beta-adrenergic action is thought to be related to the ability of the beta-adrenergic stimulants to increase the intracellular level of cyclic adenosine 3’,5’-monophosphate (cyclic AMP) in the smooth muscle (1). Recently some workers (2,3) have mentioned that papaverine, a smooth muscle relaxant, is found to strongly inhibit cyclic phosphodiesterase in rabbit aorta and rat uterus. On the other hand, Takagi, Takayanagi and Tomiyama (4, 5) have reported that the relaxing effects of papaverine and isoprenaline, a beta-adrenergic stimulant, are identical to exogenous dibutyryl cyclic AMP and that these drugs suppress a supply of calcium to the contractile protein at the membrane, Further, Takagi, Takayanagi and Tsuchida (6) have also indicated using the taenia from the guinea pig caecum that caffeine and imidazole, which influence phosphodiesterase activity, considerably modify the responses of the taenia to isoprenaline and papaverine, while the action of phenylephrine, an alpha-adrenergic stimulant, is slightly affected by caffeine and imidazole. These results indicate the possibilities that the actions of beta-adrenergic stimulants and papaverine are mediated through an increase of the intracellular level of cyclic AMP and that cyclic AMP is not concerned with the response to alpha-adrenergic stimulants.

Intracellular cyclic adenosine 3', 5'-monophosphate and relaxing effects of isoprenaline and papaverine on smooth muscle of intestine.

Abstract The beta-adrenergic action is thought to be related to the ability of the beta-adrenergic stimulants to increase the intracellular level of cyclic adenosine 3’,5’-monophosphate (cyclic AMP) in the smooth muscle (1). Recently some workers (2,3) have mentioned that papaverine, a smooth muscle relaxant, is found to strongly inhibit cyclic phosphodiesterase in rabbit aorta and rat uterus. On the other hand, Takagi, Takayanagi and Tomiyama (4, 5) have reported that the relaxing effects of papaverine and isoprenaline, a beta-adrenergic stimulant, are identical to exogenous dibutyryl cyclic AMP and that these drugs suppress a supply of calcium to the contractile protein at the membrane, Further, Takagi, Takayanagi and Tsuchida (6) have also indicated using the taenia from the guinea pig caecum that caffeine and imidazole, which influence phosphodiesterase activity, considerably modify the responses of the taenia to isoprenaline and papaverine, while the action of phenylephrine, an alpha-adrenergic stimulant, is slightly affected by caffeine and imidazole. These results indicate the possibilities that the actions of beta-adrenergic stimulants and papaverine are mediated through an increase of the intracellular level of cyclic AMP and that cyclic AMP is not concerned with the response to alpha-adrenergic stimulants.

Role of Cyclic Adenosine 3',5'-Monophosphate in the Induction of Hepatic Enzymes: III. INTERACTION OF HYDROCORTISONE AND N6,O2'-DIBUTYRYL CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE IN THE INDUCTION OF TYROSINE AMINOTRANSFERASE IN CULTURED H-4-11-E HEPATOMA CELLS

The induction of tyrosine aminotransferase in H-4-11-E hepatoma cells (a strain derived from H-35 Reuber hepatoma) in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cyclic AMP) requires low concentrations of hydrocortisone. Incubation of the cells with 10-4 m dibutyryl cyclic AMP alone failed to induce the enzyme. Hydrocortisone must be continuously present for the induction of tyrosine aminotransferase in the presence of dibutyryl cyclic AMP. The induction of tyrosine aminotransferase by 10-8 m hydrocortisone plus 10-4 m dibutyryl cyclic AMP requires both protein and RNA synthesis. Glucagon (free of insulin) alone or with hydrocortisone neither increases the adenyl cyclase activity nor induces tyrosine aminotransferase in H-4-11-E hepatoma cells. Hydrocortisone has no effect on the uptake of exogenous dibutyryl cyclic AMP and, conversely, dibutyryl cyclic AMP has no effect on the uptake of hydrocortisone. That hydrocortisone might increase the cyclic AMP-binding activity of soluble proteins has also been excluded. Hydrocortisone increases both the total activity of protein phosphokinase (or phosphokinases) of the cells and the phosphorylation in vivo of nuclear histones.