Chlorpropamide and tolbutamide inhibition of adenosine 3'5' cyclic monophosphate phosphodiesterase

These sulfonylurea agents inhibit the cyclic AMP phosphodiesterase, and thereby could increase the steady state level of cyclic AMP in various tissues, depending upon the tissue concentrations achieved after oral or parental administration.     

Effect of cyclic 3',5'-adenosine monophosphate on central neurons

In experiments on unanesthetized non-immobilized rabbits, unit responses in the cortex and thalamus to the cyclic 3',5'-adenosine monophosphate (cAMPh) were studied by means of microionophoresis. It was shown that cAMPh changes the pattern of background unit activity, increasing or decreasing the discharge frequency. cAMPh changes unit responses both to acetylcholine and noradrenaline. These data permit, to assume that cAMPh participates both in adrenergic and in acetylocholinergic mechanisms of excitation processing in brain neurones.     

Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate

The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.     

Stimulation of gibberellin-induced germination in lettuce seeds by cyclic 3',5'-adenosine monophosphate

Cyclic 3',5'-adenosine monophosphate and sodium dibutyryl cyclic3',5'-adenosine monophosphate had no effect on dark-germinationof light-sensitive lettuce {Lacluca sativa L., var. Grand Rapids)seeds when given alone. Cyclic 3',5'-adenosine monophosphate,however, synergistically enhanced the 3 µ 10^–5 Mgibberellic acid-induced germination, but showed no such effecton kinetin-stimulated germination. 5'-AMP, in contrast to cyclic3',5'-adenosine monophosphate, had no effect on gibberellicacidinduced germination. (Received August 8, 1971; )     

The action of cyclic-AMP on GA3 controlled responses III. Characteristics of barley endosperm acid phosphatase induction by gibberellic acid and cyclic 3', 5'-adenosine monophosphate

Studies on the induction of barley endosperm acid phosphataseby GA₃ and cyclic-AMP revealed (1) acid phosphatase inductionby GA₃ and cyclic-AMP is inhibited in a similar manner by ABA,cycloheximide and 6-methyl purine, (2) combinations of GA₃ andphosphodiesterase inhibitors such as caffeine and theophyllinepromoted the level of acid phosphatase induction obtainablewith the hormone alone, and (3) cyclic-AMP and GA₃ may be actingas triggers in the induction of this enzyme. Some of the implicationsof these results are discussed. (Received May 25, 1972; )     

The action of cyclic-AMP on GA3 controlled responses II. Similarities in the induction of barley endosperm ATPase activity by gibberellic acid and cyclic 3',5'-adenosine monophosphate

The effect of cyclic-AMP and GA3 on ATPase production in embryolessbarley half-seeds was examined. Similarities in the responseinduced by 5 mM cyclic-AMP and GA₃ were observed in (1) thetotal amount of ATPase produced, (2) the time course for therelease of ATPase, and (3) the effect of abscisic acid on ATPaseinduction by these compounds. Of a variety of adenine nucleotidesexamined only cyclic-AMP was found to promote high levels ofATPase activity. Some of the implications of these results arediscussed. (Received May 11, 1971; )     

Measurement of cyclic 3',5'-adenosine monophosphate synthesis in growing Escherichia coli.

The net synthesis of cAMP by an adenine auxotroph of $\text{Escherichia coli}$ was measured by assaying the incorporation of tritium from [³H]-adenine into cyclic [³H] AMP during exponential growth. Synthesis of cAMP ceased abruptly when glucose was added to cells growing in glycerol and then recovered to an intermediate rate of synthesis after 0.5–1.0 generation. Cyclic AMP appeared to be synthesized from a precursor pool that turned over more rapidly than total cellular ATP. The rates of cAMP synthesis measured by this technique are compatible with the cellular levels of cAMP previously measured in this strain(3).     

Regulation of beta-galactosidase synthesis in Escherichia coli by exogenous cyclic 3',5'-adenosine monophosphate]

The effect of cyclic 3',5'-adenosine monophosphate (cAMP) on the rate of beta-galactosidase biosynthesis was studied in the cells of Escherichia coli M-17 growing in MPB and mineral media with glucose and maltose, i.e. under the conditions of various catabolite repression, as well as upon lac-operon induction by isopropyl-beta-D-galactopyranoside (IPGP). The stimulating action of exogenous cAMP was found only in a medium with salts and glucose. The induction by IPGP was highest during the growth in a medium with glucose and maltose. When the medium contained IPGP, cAMP accelerated the enzyme synthesis in all media, but only at the early growth phases, while cAMP eliminated the effect of IPGP at the stationary phase of growth. The regulation of beta-galactosidase biosynthesis by cAMP demonstrated for the first time that this effect depended on the physiological state of E. coli: the expression of catabolite-sensitive E. coli genes was subject to both positive and negative regulation in one and the same inducible system. The effect exerted by cAMP depended on the nature of a carbon source in the growth medium.     

A simple radioimmunoassay for 3',5', cyclic adenosine monophosphate.

A radioimmunoassay for 3′,5′ cAMP has been developed in which [³H]3′,5′ cAMP is the radioligand. Antibody-bound and free fractions are separated with dextran-coated charcoal. The sensitivity of the assay is 0.03 pmoles and antiserum specificity is 7 orders with respect to other adenine nucleotides. Samples are prepared by ethanol precipitation. Tissue levels of 3′,5′ cAMP are comparable to those reported by others.     

Effect of cyclic 3',5'-adenosine monophosphate on the sporulation of Saccharomyces cerevisiae

Cyclic 3',5'-adenosine monophosphate and sodium dibutyryl cyclic3',5'-adenosine monophosphate had no effect on sporulation ofSaccharomyces cerevisiae, when added to a sporulation mediumnot enriched with glucose. They did, however, reverse the repressionof sporulation by glucose, when added to the sporulation mediumtogether with glucose. 5'-AMP, 5'-ADP and 5'-ATP did not reversethe repression of sporulation by glucose. (Received February 24, 1972; )     

Comparison of inhibition of bone resorption and escape with calcitonin and dibutyryl 3',5' cyclic adenosine monophosphate

Both parathyroid hormone (PTH) and calcitonin (CT) can increase the concentration of cyclic 3',5' adenosine monophosphate (cAMP) in fetal rat bone in organ culture. Moreover, dibutyryl cAMP (dbcAMP) can both stimulate and inhibit 45Ca release from such bones depending on dose and experimental conditions. In this study we compared dbcAMP and CT for their effects on bones pretreated with PTH. Both compounds produced transient inhibition of bone resorption followed by escape. Escape from dbcAMP was independent of prostaglandin synthesis, since it occurred both in the presence and absence of indomethacin, a prostaglandin cyclo-oxygenase inhibitor.