Re: Parasite Kill with Caffeine?

Does everyone have to check in with you beore posting a question?

F U


http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003155#re...



Fast Inhibition of Glutamate-Activated Currents by Caffeine

Conclusions

We have demonstrated a novel action of caffeine on excitatory transmission in the central nervous system. We show that, in addition to increasing the probability of spontaneous release of neurotransmitter, caffeine inhibits postsynaptic AMPA-type glutamate-activated channels. This occurred at caffeine concentrations regularly used for studying intracellular calcium signaling. Furthermore, our results are consistent with the hypothesis that caffeine-mediated glutamate receptor blockade may only occur under extreme conditions of toxicity



http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003586


Molecular Cloning and Characterization of Novel Glutamate-Gated Chloride Channel Subunits from Schistosoma mansoni
Author Summary

Schistosomiasis is a debilitating disease caused by blood flukes in the genus Schistosoma that afflicts over 200 million people worldwide. Treatment relies almost exclusively on a single drug, praziquantel. Reports of sub-optimal efficacy of praziquantel raise concerns about the prospect of drug resistance and highlight the need to develop new schistosomicidal drugs. Neuroactive receptors are recognized targets of insecticides and anthelmintics. Likewise, neuroyhb nal receptors of schistosomes are attractive targets for drug development. Lacking a coelom and a proper circulatory system, schistosomes are thought to lack the capacity for endocrine signaling, and therefore depend entirely on neuronal modulation to control functions vital to their survival and reproduction. We characterized a novel family of glutamate-gated chloride channel (GluCl) receptors from S. mansoni that are pharmacologically and evolutionarily distinct from GluCls in nematodes, insects and snails. Our phylogenetic analyses suggest that these receptors are also widely distributed in other flukes and tapeworms. This study provides the first molecular evidence for the contribution of an inhibitory component to glutamatergic signaling in S. mansoni. Our findings add to a growing body of evidence suggesting that glutamatergic signaling in schistosomes may be physiologically important, and could be targeted for chemotherapeutic intervention.




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