Cross-inhibition

Cross-inhibition, which decreases the biodegradation rate of the multiple targeted compounds. 

Since IFN- and IFN-a bind to the same receptor, the ability of the IFN- synthetic peptides to block both bovine and human IFN-a was examined. Interestingly, only three of the four inhibitory peptides were effective competitors of IFN-a. Cross-inhibition of IFN-a by the internal and carboxy-terminal peptides was observed and suggested that these residues may adopt a similar conformation in both molecules and bind to a common site on the receptor. The aminoterminal peptide failed to reduce IFN-a function entirely. Thus, either the IFN-a amino-terminus has a much higher affinity for receptor or the IFN- aminoterminus binds a unique site on the receptor complex that may be associated with its unique properties. As expected, none of the peptides blocked the antiviral activity of IFN- , which interacts with a different receptor. 

The whole question of the specificity was reopened with the discovery that E. coli phosphatase, contrary to an earlier statement (114), hydrolyzed a variety of polyphosphates including metaphosphate of average chain length 8 (97). It was subsequently reported that partially purified phosphatases from several mammalian tissues had appreciable PPi-ase activity at pH 8.5 (115). This was confirmed (116) and extended to include ATPase and fluorophosphatase activities (117). Proof that the same enzyme is responsible for the monoesterase and PPi-ase activities was afforded by heat inactivation studies, cross inhibition experiments, and inhibition of PPi-ase activity by L-phenylalanine, a specific inhibitor of intestinal phosphatase. It was also found that calf intestinal phosphatase couid be phosphorylated by 32P-PP and the number of sites so labeled agreed with the number of active sites determined with a monoester substrate using a stopped-flow technique (118). It would seem that the main reason for the confusion with regard to the PPi-ase activity results from the inclusion of Mg2+ in the assay. This stimulates the monoesterase activity but almost completely inhibits PPi-ase activity (117). 

Khakh BS, Zhou X, Sydes J, Galligan JJ, Lester HA (2000) State-dependent cross-inhibition between transmitter-gated cation channels. Nature 406 405-10 Khakh BS, Gittermann D, Cockayne DA, Jones A (2003) ATP Modulation of excitatory synapses onto interneurons. J Neurosci 23 7426-37... 

As already implied by the above scheme, it is essential that chiral amplification and symmetry breaking comprising the generic autocatalytic steps A + R -> 2R and A+S 2S, require some sort of cross-inhibition between the two enantiomers, for instance expressed by R + S —> P. Here A denotes an achiral substrate and P an unspecified product. In the absence of crossinhibition, the ee will at best stay at its initial value but amplification remains impossible [66]. 

Lente proposed a discrete-state stochastic modeling approach in which chiral amplification could be described by a quadratic autocatalytic model without considering cross-inhibition [67,68]. However, the discrepancy between the usually employed deterministic kinetic approach, which reinforces the need for cross-inhibition, and the discrete-state stochastic approach is only apparent. The discrete approach considers the repetitive reproduction of single molecules which, in the case of a chiral system, obviously are individually all enantiomerically pure. Hence, basically no amplification of the ee occurs at all during the discrete scenario. It has been indicated that deter-... 

The visual effects associated with the PDE-5 inhibitor therapies are consistent with cross-inhibition of the enzyme PDE-6, which is involved in retinal phototransduction. 

There is some evidence for mutual cross-inhibition of proliferation and cytokine secretion by ThI and Th2 T lymphocytes, which is mediated by particular cytokines. For example, exogenous IL-4 favours the growth and proliferation of Th2 T lymphocytes, whereas Th2 clones are exquisitely sensitive to inhibition by IFNy. IL-2 is a growth factor for both ThI and Th2 cells. Whereas in mice, IL-10 significantly inhibits the proliferation and cytokine secretion of ThI cells (Fiorentino etal., 1989), human IL-10 significantly inhibits proliferation of and cytokine secretion by both ThI and Th2 clones raised in response to specific antigen or lectin, and is itself a... 

Hill M, et al. (2005). Heme oxygenase-1 inhibits rat and human breast cancer cell proliferation Mutual cross inhibition with indoleamine 2,3-dioxygenase. Faseb J. 19(14) 1957-1968. 

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