Dibutyryl Cyclic 3 , 5 -AMP

Ping L, Kimihiro M, Tohru Y, Yasushi O. Nardosinone, the first enhancer of neurite outgrowth-promoting activity of staurosporine and dibutyryl cyclic AMP in PCI 2D cells. Dev Brain Res 2003 145 177-183. 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

Schulz, M., Hamprecht, B., Kleinkauf, H., and Bauer, K. (1989). Regulation by dibutyryl cyclic AMP of carnosine synthesis in astroglial-rich primary cultures kept in serum-free medium. J. Neurochem. 52, 229-234. 

Calmodulin-dependent phosphodiesterase = Dibutyryl cyclic AMP = Acyl carrier protein = S-Adenosyl-L-methionine = S-Adenosyl-I-homocysteine... 

Reeves JJ, Jones CA, Sheehan MJ, Vardey CJ, Whelan CJ (1997) Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo. Inflamm Res 46(5) 180-184 Ribeiro JA, Walker J (1975) The effects of adenosine triphosphate and adenosine diphosphate on transmission at the rat and frog neuromuscular junctions. Br J Pharmacol 54(2) 213-218 Ribeiro JA, Sebastiao AM (1984) Enhancement of tetrodotoxin-induced axonal blockade by adenosine, adenosine analogues, dibutyryl cyclic AMP and methylxanthines in the frog sciatic nerve. Br J Pharmacol 83(2) 485—492... 

The results on the first two enzymes, and on the others, are from Brebnor et al.(26), and from Greengard and Cayanis(23), respectively. For increases and decreases (plus and minus signs) under "Immature rats" see refs 8 and 25. DcAMP, dibutyryl cyclic AMP N.S., no significant change. 

In Table II of his comments, Dr. Laduron points out differences between bovine and human parathyroid cells. Several of these are in error. Prostaglandins affect both human and bovine parathyroid cells. Phosphodiesterase inhibitors have not been tested directly in human parathyroid cells, although dibutyryl cyclic AMP, which may act in part by inhibiting phosphodiesterase, stimulated PTH release in fragments of human parathyroid glands (6). 

Activation of neostriatal tyrosine hydroxylase was observed when cyclic AMP was added to high speed supernatants from rat neostriatum (133). Intraventricular injection of dibutyryl cyclic AMP stimulated tyrosine hydroxylation in the neostriatum (134). However, it is still questionable if under physiological conditions this cyclic AMP involvement in the feedback control of tyrosine hydroxylase activity is mediated by presynaptic dopamine receptors or by presynaptic allo-receptors. In addition, if a dopamine sensitive adenylate cyclase is involved in the regulation of neostriatal tyrosine hydroxylase activity it is relevant to know if this adenylate cyclase is linked to a D-1 and/or a D-2 receptor. At this point in time experimental data are not in favour of the presence of a D-l receptor linked to an adeiylate cyclase on the varicosities of dopaminergic neurons in the neostriatum. E.g. concentrations of dopamine agonists stimulating cyclic AMP formation inhibit tyrosine... 

Cyclic AMP is one of the mediators of FSH action on LH receptor induction because dibutyryl cyclic AMP will increase granulosa receptors in vitro. Other factors may also be involved (e.g., oestrogens) because the cyclic AMP analogues were less potent than FSH. Once induced, the continual presence of FSH is required to maintain normal levels of LH receptors [5],... 

Hunzicker-Dunn et al. [73] and Ezra and Salomon [74] suggested that the desensitization of the ovarian adenylate cyclase system by LH involves a phosphorylation reaction. The latter may alter the conformation of the receptor and/or Gs. If phosphorylation is the mechanism it may well be mediated by protein kinase C because phorbol esters, which are presumed to activate this enzyme, mimic LH induced desensitization in Leydig tumour cells [75,76]. There are, however, differences between LH- and phorbol ester induced desensitization [76], Cyclic AMP-dependent protein kinase is probably not involved because dibutyryl cyclic AMP does not mimic LH induced desensitization in Leydig cells [70]. 

Page94,figure 10.8 LifeSci. 32 191-95(1983),Nakaki,T. et al. Inhibition of dibutyryl cyclic AMP-induced insulin release by alpha-2 adrenergic stimulation. Reprinted with permission from Elsevier. 

Catecholamines inhibit phosphodiesterase from beef heart [44] and guinea-pig lung [45], and so does N, 2 -0-dibutyryl cyclic AMP [47] which has been used to mimic cyclic AMP effects as it is more lipid-soluble and, therefore, assumed to penetrate cell membranes more readily than cyclic AMP [6,46]. A large number of other drugs inhibit the phosphodiesterase activity of rat brain and cat heart [48]. 

Protein kinase does not bind either Af ,2 -0-dibutyryl cyclic AMP [74], which has been employed to mimic cyclic AMP effects [6], or I-succinyl cyclic nucleotide tyrosine methylester [83], which is used in the radioimmunoassay of cyclic nucleotides [84]. 

In less well controlled studies topical theophylline, with or without topical dibutyryl cyclic AMP or a cyclic AMP analog, has shown modest efficacy in psoriasis.29,30 An uncontrolled clinical trial of oral theophylline is said to have demonstrated beneficial results in psoriasis.31 In two uncontrolled clinical studies of intramuscular dibutyryl cyclic AMP, studies inspired by our earlier biochemical studies on cyclic nucleotides in psoriasis,Chinese physicians in Shanghai considered the drug effective in 80% of 69 patients treated.32,33 in the Chinese studies, reported side effects were insignificant and thus it should be possible to duplicate their study but using a double blind design. In view of the excellent re-... 

In 1962 Klainer et al. (K4) reported that TSH increased the amount of cyclic AMP in incubated sheep thyroid particulate fractions by 25-35%. Gilman and Rail (Gl) reported that TSH increased the level of cyclic AMP in incubated bovine thyroid slices. Cyclic AMP itself is not a good stimulator of CO2 production from glucose in some thyroid preparations. This may be due to inactivation of cyclic AMP by phosphodiesterase (P6). However, an analog of cyclic AMP, dibutyryl cyclic AMP, will enhance the conversion glucose-l- C to CO2 (PI). Hie dibu-... 

Goodman, R., Oesch, F. and Thoenen, H. (1974) Changes in enzyme patterns produced by high potassium concentration and dibutyryl cyclic AMP in organ cultures of sympathetic ganglia. J. Neurochem. 23 369-378. 

Keen, P. and McLean, W.G. (1974) Effect of dibutyryl-cyclic AMP and dexamethasone on noradrenaline synthesis in isolated superior cervical ganglia. J. Neurochem. 22 5-10. 

Mackay, A.V. and Iversen, L.L. (1972) Increased tyrosine hydroxylase activity of sympathetic ganglia cultured in the presence of dibutyryl cyclic AMP. Brain Res. 48 424—426. 

Neuron-like cell lines are attractive models for exploring in vitw ncurotoxicology because they proliferate rapidly in their undifferentiated state, and many of them can be induced to develop propertic.s of more mature neurons (i.e., differentiate) with stimulants such as dibutyryl cyclic AMP (dBcAMP), retinoic acid, or NGF.. Several neuronal cell lines have been studied for more than 30 years and found to have neurobiological properties these cells thus provide well-characterizcd models for specific toxicologic investigations. Mouse, rat, and human cell lines are commonly used for in vitro neurotoxicity te.sting because of their stability and hardiness. 

Labourdette, G., and Mandel, P. (1980). Effect of norepinephrine and dibutyryl cyclic AMP on S-lOO protein level in C6 glioma cells. Biochem. Biophvs. Res. Commun. 96, 1702-1709. 

While muscle cells in tissue culture can be stimulated to break down glycogen only minimally when incubated in a solution containing cyclic AMP, they are more readily stimulated by compounds like dibutyryl cyclic AMP, whose structure is shown in Figure 21.4. 

Imai Y, Ibaraki K, Odajima R, Shishiba Y. Effects of dibutyryl cyclic AMP on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts in culture. Endocr J 1994 41 645-654. 

Figure 12. Concentration-response relationship for the action of dibutyryl cyclic AMP on histamine release induced by antigen (22% of total in the absence of dibutyryl cyclic AMP) (O—O) and A23187 (77% of total in the absence of dibutyryl cyclic AMP) (" —0). Cells with or without dibutyryl cyclic AMP were incubated for 30 min before the addition of the histamine release agent ( 54).

Figure 13. Inhibition by dibutyryl cyclic AMP and theophylline of antigen-induced 4S-Ca uptake Cn and A23187-induced 45-Ca uptake (U) Mo rat mast cells. Uninhibited values from which percent inhibition was calculated were 3150 300 cpm/10 cells and 5550 350 cpm/l(P cells for 45-Ca uptake induced by antigen and A23187, respectively. Corresponding histamine releases were 43 11% and 62 2% (37).

Inhibition of Calcium Movement. Figure 15 shows that cromoglycate inhibits membrane permeability to 45-calclum over the same concentration range for the inhibition of histamine release. Furthermore when cromoglycate was compared with dibutyryl cyclic AMP and doxantrazole, the relative potencies of the drugs for inhibition of histamine release (doxantrazole cromoglycate dibutyryl... 

Figure 15. Inhibition by doxanlrazole, cromoglycate, and dibutyryl cyclic AMP of 45-Ca uptake induced by antigen (filled symbols) or A23187 (open symbols). The 45-Ca uptakes in the absence of inhibitor were 924 cpm/W cells for antigen and 5274 cpm/W cells for A231. Corresponding hikamine secretions were...

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