Effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5'-monophosphate.

The effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5' monophosphate levels (cyclic AMP) was studied in twelve healthy subjects. Plasma cyclic AMP levels were found to be markedly elevated without significant changes in urinary cyclic AMP or cyclic AMP/creatine ratio. Most likely altered plasma glucagon and catecholamine levels were responsible for these changes.     

Stimuli which provoke secretion of azurophil enzymes from human neutrophils induce increments in adenosine cyclic 3'-5'-monophosphate

1. Stimuli for human neutrophils were divided into two classes on the basis of their ability to induce degranulation: complete secretagogues provoked release of both azurophil and specific granules, while incomplete secretagogues only induced release of specific granules. 2. Complete secretagogues, which possessed the ability to induce secretion of azurophil granules, also induced transient increments in total cellular cyclic AMP levels: incomplete secretagogues did not. 3. Complete secretagogues, unlike the incomplete variety, also induced further increments of cyclic AMP in prostaglandin E1-pretreated neutrophils. 4. Inhibition of lysosomal enzyme release by prostaglandin E1 was closely correlated with elevated levels of cyclic AMP induced by the prostaglandin alone, than with the much higher transient increment in cyclic AMP produced by stimulation of prostaglandin E1-treated cells. 5. Our results describe the first biochemical difference between neutrophil responses associated with secretion of azurophil granules, as opposed to specific granules: transient increments in cyclic AMP.     

Effect of Ricinus communis toxin on cyclic adenosine 3':5'-monophosphate metabolism in Yoshida ascites sarcoma cells.

Prostaglandin E1 (2.5 mug/ml) enhanced the level of cyclic adenosine 3':5'-monophosphate (cyclic AMP) three to four times in Yoshida ascites sarcoma (YS) cells cultured in vitro. When Ricinus communis toxin (RC-toxin) was added 30 min after the addition of prostaglandin E1, the enhanced level of cyclic AMP in the YS cells decreased rapidly. Of RC-toxin, 0.2 mug/ml was enough to produce the maximum effect. By addition of 5 mM lactose with RC-toxin, approximately 60% of the RC-toxin effect on the levels of cyclic AMP was abolished. This indicates that the specific binding of RC-toxin on the surface membrane is largely responsible for the observed decrease of the cyclic AMP level. The toxin treatment did not induce either leakage of cyclic AMP from the cell or change in the activity of cyclic AMP phosphodiesterase. However, the treatment of YS cells with RC-toxin caused a decrease of adenylate cyclase activity when the activity was measured at a substrate concentration of 0.15 mM ATP. In contrast, there was little difference with the control when the activity was assayed at a higher ATP concentration, 0.24 mM. It was found that the K-m of adenylate cyclase for ATP was changed by RC-toxin from 0.1 to 0.25 mM, and that the Mg2+ activation of the enzyme observable in untreated cells disappeared. These results suggested that the decrease in the level of cyclic AMP in YS cells induced by RC-toxin can be explained in terms of the change in K-m of the adenylate cyclase activity.     

Induction of hepatic tyrosine aminotransferase in vivo by derivatives of cyclic adenosine 3':5'-monophosphate.

A number of 8- and N6-SUBSTITUTED DERIVATIVES OF CYCLIC ADENOSINE 3':5'-MONOPHOSPHATE-DEPENDENT PROTEIN KINASE, AND AS SUBSTRATES FOR RAT LIVER CYCLIC NUCLEOTIDE PHOSPHODIESTERASE. All of the analogs tested were able to induce the transaminase. The induction by the analogs was shown to be the result of an actual increase in the amount of enzyme, and the mechanism of induction was an increase in the rate of synthesis of the transaminase. The induced enzyme appeared to be immunologically similar to the non-induced enzyme. A good correlation was found to exist between the dose that produced 50% of maximal induction and a combination of the activation constant for cyclic adenosine 3':5'-monophosphate-dependent protein kinase by the analog and its susceptibility to hydrolysis by cyclic nucleotide phosphodiesterase. These data suggest that the phosphorylation of some site is involved in the mechanism by which cyclic adenosine 3':5'-monophosphate affects the rate of synthesis of tyrosine aminotransferase.