Adenosine monophosphate accumulation

Adenosine deaminase (ADA) was the first therapeutic enzyme coupled to PEG with the aim of reducing clearance and thereby overcoming the short half-life of ADA. Patients deficient in ADA are unable to regulate purine metabolism. As a result purine metabolites (e.g., adenosine monophosphate) accumulate to cytotoxic levels in B-lymphocytes and lead to severe B-cell depletion that presents clinically as severe combined immunodeficiency syndrome (SCIDS). While intramuscular injection of unmodified ADA provides some relief, antibodies develop rapidly against the protein and prevent it from being useful as replacement therapy. Even in the absence of antibodies, unmodified ADA s plasma half-life is only a few minutes. 

Brown, EM, Fuleihan, Ge-H, Chen, CJ and Kifor, O, 1990, A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3, 5 -cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells, Endocrinology 127 1064-1071... 

Shimizu M, Nishida A, Zensho H, Yamawaki S. Chronic antidepressant exposure enhances 5-hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes. J Pharmacol Exp Ther 1996 279 1551-1558. 

M19. Mitra, S. P., and Carraway, R. E., Synergistic effects of neurotensin and beta-adrenergic agonist on 3,5-cyclic adenosine monophosphate accumulation and DNA synthesis in prostate cancer PC3 cells. Biochem. Pharmacol. 57, 1391-1397 (1999). 

B7. Borgeat, P., Chavancy, G., Dupont, A., Labrie, F., Arimura, A., and Schally, A. V., Stimulation of 3 5 -cydic adenosine monophosphate accumulation in anterior pituitary gland in vitro by synthetic luteinizing hormone releasing hormone. Proc. Nat. Acad. Sci. U.S. 69,2677-2681 (1972). 

FI. Fain, J. N., Pointer, R. H., and Ward, W. F., Effects of adenosine nudecisides on adenylate cyclase, phosphodiest-erase, cyclic adenosine monophosphate accumulation, and lipolysis in fat cells. /. Biol. Chem. 247, 6866 (1972). 

Brown, E. M., Gardner, D. G., Windeck, R. A., and Aurbach, G. D., 1979, Cholera toxin stimulates 3, 5 -adenosine monophosphate accumulation and parathyroid hormone release from dispersed bovine parathyroid glands. Endocrinology 104 218. 

Fig. 6.4 In vitro effects of mutation on desensitization and internalization of the dopamine receptor. Shown here are effects of mutation on dose-dependent intracellular cyclic adenosine monophosphate (cAMP) accumulation (A and B) and binding curves (C and D) for artificial ligand (SCH 23390) using three constructs controls (wild type, A and C) and the Thr360Ala mutant (360, B and D). In the desensitization experiments, cells were preincubated with 10 oA/ dopamine (o) or vehicle ( ) for 20min, and increasing concentrations of dopamine (10 to 10 (iM) were added to assess cAMP accumulation. Note that loss of efficacy and potency seen in wild-type cells (A) disappeared with the Thr360Ala mutation (B). Conversely, internalization, assessed by decrease in SCH23390 binding (C) after pretreatment with lOpM dopamine (o, compared to vehicle ), was essentially unchanged by the Thr360Ala mutation (D)...

MTX also has several effects on the purine synthetic pathway. MTXPGs inhibit the enzyme aminoimidazole carboxamide ribonucleotide (AlCAR) transformylase, which in turn causes intracellular accumulation of AICAR. AICAR and its metabolites can then inhibit two enzymes in the adenosine pathway adenosine deaminase and adenosine monophosphate (AMP) deaminase, which leads to intracellnlar accumulation of adenosine and adenine nucleotides. Subsequent dephosphorylation of these nucleotides results in increased extracellular concentrations of adenosine, which is a powerful anti-inflammatory agent (11). 

Uterine relaxation is mediated in part through inhibition of MLCK. This inhibition results from the phosphorylation of MLCK that follows the stimulation of myometrial (3-adrenoceptors relaxation involves the activity of a cyclic adenosine monophosphate (cAMP) mediated protein kinase, accumulation of Ca++ in the sarcoplasmic reticulum, and a decrease in cytoplasmic Ca. Other circulating substances that favor quiescence of uterine smooth muscle include progesterone, which increases throughout pregnancy, and possibly prostacyclin. Progesterone s action probably involves hyperpolarization of the muscle cell membrane, reduction of impulse conduction in muscle cells, and increased calcium binding to the sarcoplasmic reticulum. 

Mechanism of Action A blood modifier and platelet aggregation inhibitor that inhibits the activity of adenosine deaminase and phosphodiesterase, enzymes causing accumulation of adenosine and cyclic adenosine monophosphate. Therapeutic Effect Inhibits platelet aggregation may cause coronary vasodilation. 

It has been long recognized that prolonged lithium therapy can cause hypothyroidism. In fact, determination of serum thyroid-stimulating hormone once a year is recommended in all subjects on prolonged lithium therapy [32, 33]. Lithium perturbs receptor-mediated signaling events such as cyclic adenosine monophosphate and inositol phosphate accumulation [34]. These effects likely explain many hormonal side effects of lithium. 

Still about saponin 1,87, isolated from A. membranaceus, Zhang et al. [317] report that this substance induces the accumulation of cyclic adenosine monophosphate (cAMP) and cyclic guanidine monophosphate (cGMP) in rabbit plasma and affects DNA biosynthesis in partially... 

Case Study Changes in Potency Caused by Lot-to-Lot Differences in CAMP In this example, THP-1 cells (a human leukemia cell line) were found to be responsive to a biotherapeutic agent in development. The biotherapeutic caused a stimulation of cAMP that accumulated in the cells exposed to drug and could be released after lysing the cells. Therefore, determination of cyclic adenosine monophosphate (cAMP) levels in THP-1 cell culture lysates was used as an indicator... 

It is a well-recognized CNS-drug which action is solely attributed on account of its inhibition of the enzyme phosphodiesterase in the brain and the ultimate accumulation and actions of cyclic 3, 5 -adenosine monophosphate (C-AMP). 

The very existence of a receptor for cannabinoids like A -tetrahydrocannabi-nol (THC) was debated prior to 1990, but compelUng evidence for this receptor was reported in the late 1980s by the laboratory of Dr. Allyn Howlett. They demonstrated cell-specific inhibition of cyclic adenosine monophosphate (cAMP) accumulation (1) and guanylyhmidodiphosphate (GPP-NH-P)-sensi-tive binding of a tritium-labeled CP55940 to rat brain membranes (2), implying... 

They competitively antegonize cellular adenosir receptors, resulting in CNS stimulation, vasoconstriction, and tachycardia and the accumulation of cyclic nucleotides [especially cyclic adenosine monophosphate (cAMP)]. 

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