Three austin family compounds from Penicillium brasilianum exhibit selective blocking action on cockroach nicotinic acetylcholine receptors

Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan.
NeuroToxicology (Impact Factor: 3.38). 10/2010; 32(1):123-9. DOI: 10.1016/j.neuro.2010.10.003
Source: PubMed

ABSTRACT Austin (AT) and its derivatives (dehydroaustin (DAT) and acetoxydehydroaustin (ADAT)) produced by Penicillium brasilianum MG-11 exhibit toxicity to insects, yet their targets are unknown. Here, we used whole-cell patch-clamp electrophysiology to investigate the action of AT family compounds on cockroach acetylcholine (ACh), γ-aminobutyric acid (GABA) and l-glutamate receptors expressed in the American cockroach (Periplaneta americana) neuron. U-tube application of AT or its derivatives did not induce any current amplitudes, suggesting that they did not act as agonist of these three receptors. In the second step of experiments, they were bath-applied for 1min before co-application with the corresponding ligand. We found that AT and its derivatives had no effect on GABA and l-glutamate-induced currents, whereas they significantly reduced ACh- and epibatidine-induced currents, showing that these compounds acted as selective antagonists of nicotinic acetylcholine receptors (nAChRs) expressed in the cockroach neuron. Of the compounds, DAT showed the highest blocking potency for nAChRs, differentially attenuating the peak and slowly desensitizing current amplitude of ACh-induced responses with pIC(50) (=-logIC(50) (M)) values of 6.11 and 5.91, respectively. DAT reduced the maximum normalized response to ACh without a significant shift in EC(50), suggesting that the blocking action is not competitive with ACh.

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    • "The polyketide synthase gene, ausA, is involved in the formation of meroterpenoids, austinol and dehydroaustinol [37]. Related compounds isolated from Penicilliumbrasilianum appear to have insecticidal properties [38]. Given that A. nidulans harbours many more verified and putative secondary metabolite pathways [39] more biosynthetic genes and their regulatory elements might be activated by D. melanogaster fungivory. "
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    • "Austin-like compounds 9–12 represent a class of meroterpenoids mainly isolated from Aspergillus and Penicillium genera (Chexal et al., 1976; Schurmann et al., 2010; Geris dos Santos and Rodrigues-Filho, 2002, 2003). It was previously reported that these derivatives exert notable toxicities to insects (Geris et al., 2008; Hayashi et al., 1994) and the very recently a blocking action on cockroach nicotinic acetylcholine receptors was demonstrated for compounds 9, 11 and 12 (Kataoka et al., 2011). In view of this, Emericella sp. "
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