The in vivo stimulation of rat liver ornithine decarboxylase activity by dibutyryl cyclic adenosine 3',5'-monophosphate, theophylline and dexamethasone

The hepatic ornithine decarboxylase (ODC) activity of normal rats was stimulated more than 7-fold 3 hours after a single intraperitoneal injection of dibutyryl cyclic adenosine 3′,5′-monophosphate (dibu-cAMP). The 3-hour ODC activity was also stimulated by single injections of either theophylline or dexamethasone (10- and 21-fold, respectively). The simultaneous administration of actinomycin D with either dibu-cAMP, theophylline or dexamethasone reduced the 3-hour ODC activity by 91, 62 and 58 percent, respectively. When actinomycin D was given one hour after dibu-cAMP, no inhibition of ODC activity was observed.     

Inhibition by interferon (alpha + beta) of mouse liver regeneration and its reversal by putrescine

Mouse interferon (alpha + beta) given to mice by intraperitoneal injection suppressed both the accumulation of putrescine and stimulation of DNA synthesis in liver caused by partial hepatectomy. The suppression of DNA synthesis was completely reversed by exogenous putrescine. The same results were obtained when core 2',5'-oligoadenylate instead of interferon was given to partially hepatectomized mice. These results suggest that interferon inhibits putrescine formation through elevating the 2',5'-oligoadenylate level and thus inhibits DNA synthesis in the regenerating liver.     

Implantation in ovariectomized mice treated with dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP).

Experiments are described that demonstrate that uterine intraluminal injection of a 1-25 mM-solution of dibutyryl cyclic AMP (dcAMP) in phosphate buffered saline (PBS) induced implantation in ovariectomized pregnant mice. Pretreatment with progesterone was essential for this effect. When PBS was injected alone, it did not induce implantation in mice treated with progesterone. Bilateral adrenalectomy had no effect on the ability of dcAMP to substitute for oestradiol, showing that the effect was not due to dcAMP-induced oestrogen synthesis in the adrenal cortex. It is suggested that the dcAMP may act at the level of the uterus, the embryo, or both.     

Inhibition of Escherichia coli growth by cyclic adenosine 3', 5'-monophosphate

Cyclic AMP inhibits growth rate of E. coli Hfr 3000. Doubling times in glucose minimal medium increased from 60 to about 90 minutes with the addition of 5 mM cAMP. This effect is specific since it was not observed when the cyclic nucleotide was replaced by 5′ AMP, ADP, ATP or adenosine. Half maximal inhibition was obtained with 1 to 3 mM cyclic AMP. This inhibition occurs only with those carbon sources which are known to decrease intracellular cyclic AMP levels, i.e. glucose and pyruvate. No inhibition was observed with succinate, malate or glycerol.     

Inhibition of adenosine 3',5'-monophosphate phosphodiesterase by nicotinamide and its homologues in vitro.

Inhibition of cAMP phosphodiesterase from rat liver by nicotinamide and its homologues was studied. Among the several compounds tested, such agents as nicotinamide, N2-ethylnicotinamide, N2-methylnicotinamide, N,N-diethylnicotinamide, 3-acetylpyridine, methylnicotinate, and ethylnicotinate showed potent inhibition of cAMP phosphodiesterase, with an over 90% inhibition by 5 mM ethylnicotinate when cAMP was used as substrate at a 0.48 x 10(-7) M concentration. A comparison of the inhibitory curves of theophylline, papaverine, and ethylnicotinate on enzyme activity showed them to be approximately coincident. Furthermore, the plots with abscissa of equal increments per concentration of ethylnicotinate in the presence of theophylline or papaverine coincided with that in the absence of these agents.     

Avidin induction by dibutyryl cyclic guanosine 3',5'-monophosphate in chick oviduct organ culture

A progesterone-dependent protein, avidin, was induced by dibutyryl cGMP in a dose-dependent manner in chick oviduct organ culture. A four-fold concentration of avidin over the control samples was observed with a concentration of dibutyryl cGMP of 1 mM. The time course of avidin accumulation was essentially similar to that caused by progesterone. Dibutyryl cAMP at the same concentration had no effect on the avidin concentration in the cultured oviduct tissue or medium. These results suggest a possible role of cGMP in avidin induction or in the modulation of avidin synthesis.