Adenylate cyclase toxic

Caffeine is also effective in the antagonism of peripheral adenosine (type I) receptors, which are known to inhibit lipolysis by subduing adenylate cyclase activity.28 The appeal of this mechanism of action is that the majority of the pharmacological effects of adenosine on the central nervous system can be inhibited by doses of caffeine that are well within physiologically non-toxic levels comparable to only a couple of cups of coffee.5... 

Some bacteria produce effects similar to those of cholera toxin in different ways. For example, among a variety of toxic proteins produced by Bacillus anthracis, the causative agent of anthrax, is an adenylate cyclase that is able to enter the host s cells.s Similarly, B. pertussis, in addition to... 

SAM) 591,592s, 813, 875 decarboxylation 753, 754 reaction with catechol O-methyltransferase 592 Adenosyltransferase, B12s 870 Adenoviruses 247, 346 Adenylate cyclase 556-557, 556s, 657 characterization of 556 toxic 548... 

As already mentioned (see section 3.1) lipid peroxides can also break down non-enzymically to yield a variety of carbonyls, such as the hydroxyalkenals [54]. These aldehydes, and in particular 4-hydroxynonenal (HNE), can react with thiol and amino groups of nearby proteins, affecting several enzymic activities [55], These effects however appear to occur at HNE concentrations greater than 10 [lM. At low non-toxic concentrations other effects have been observed which have considerable relevance to cell proliferation. These include the stimulation of adenyl-cyclase and phospholipase C activity in liver membranes [56,57] and an inhibition of ornithine-decarboxylase activity [58] and the expression of globin genes and the protooncogene c-myc in K562 murine leukaemia cells [59]. 

Anthrax toxin is composed of three proteins protective antigen (PA 83kDa), lethal factor (LF 90kDa), and edema factor (EF 89kDa). Individually, none of the three proteins are toxic but interact synergistically with at least one of the others. PA and LF (called LeTx) can cause lethal shock in experimental animals, and a mixture of PA and EF (edema toxin, EdTx) induces edema at the site of injection. Since two discrete units of the toxin are required for its action, the term binary toxin has been used to this and other bacterial toxins. Anthrax is unique from other binary toxins in that the binary moieties (EF and LF) interact only after being secreted from the bacteria. Further, EF and LF enter the cell via a single PA protein. Assembly of the three toxin proteins is initiated when PA binds to a proteinaceous cellular receptor and is activated by a member of the furin family of cellular proteases. The exact mechanisms of internalization of the toxin moieties are subject of scientific enquiry. Inside the cellular cytoplasm, EF (a calcium and calmodulin-dependent adenylate cyclase) causes a dramatic increase in intracellular cAMP concentrations and LF acts proteolytically to cleave certain MAPK kinases. 

Lithium is one of the group lA alkali metals (like potassium and sodium) and is not normally present in the body. It acts predominantly through the phosphatidylinositol (PI) second messenger system, causing alterations in calcium- and protein kinase C (PKC)-mediated processes. Lithium can also alter the adenylate cyclase (AC) system, but this action is probably related to its toxic effects. Many calcium-dependent systems may be affected by lithium, among them regulation of receptor sensitivity, parathyroid hormone release, and proper functioning of intracellular microtubule structures. - ... 

Cannabis acts as an agonist at the CB1 cannabinoid receptor, which is the only one known to date to be expressed in the brain. It is particularly distributed in the frontal regions, the basal ganglia, the cerebellum, and the limbic forebrain (particularly in the hypothalamus and in the anterior cingulated cortex). The relative scarcity of cannabinoid receptors in the brainstem nuclei may account for the low toxicity of cannabis when given in overdose. A second cannabinoid receptor, CB2, is expressed only in the peripheral immune system. Both cannabinoid receptors are members of the G-protein-coupled class, and their activation is linked to inhibition of adenylate cyclase activity. 

Edema Toxin (EdTx) and Lethal Toxin (LeTx) are two toxins with immunomodulatory activity that are produced by A anthracis, the cause of the disease anthrax. Both toxins are composed of a heptameric complex of protective antigen (PA) bound to either edema factor (EF) or lethal factor (LF). " The heptameric complex of PA is responsible for receptor binding and cellular entry, whereas toxicity is associated with both EF, a calmodulin-dependent adenylate cyclase that induces increases in cytosolic cAMP and LF, a metalloprotease that cleaves mitogen-activated protein kinase kinases (MAPKK). ... 

An unusual glycoside, wedeloside (96), from Wedelia asperrima (Asteraceae), inhibits mitochondrial ADP/ATP carrier protein and has the ability to protect animals against the toxic effects of aflatoxin Bi (Croteau and Johnson, 1985 Node et al., 1982). Uie diterpene forskolin (97), from Coleus barbatus and C. forskohlii (Lamiaceae), is an activator of adenylate cyclase, and is an active inhibitor of the action of brefeldin A (a fungal metabolite with pronounced effects on protein trafficking in cells) (De Sousa and Shah, 1988 Schreiber, 1992 Valdes et al., 1987 Wagner, 1988). This compound also is of interest as an antihypertensive agent (Alcaraz and Rios, 1991 Hanson, 1991). 

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