tailieunhanh - Báo cáo Y học: Amphibian peptides that inhibit neuronal nitric oxide synthase The isolation of lesueurin from the skin secretion of the Australian Stony Creek Frog Litoria lesueuri

Two neuropeptides have been isolated and identi®ed from the secretions of the skin glands of the Stony Creek Frog Litoria lesueuri. The ®rst of these, the known neuropeptide caerulein , is a common constituent of anuran skin secretions, and has the sequence pEQY(SO3 )TGWMDF-NH2 . This neuropeptide is smooth muscle active, an anal-gaesic more potent thanmorphine and is also thought to be a hormone. | Eur. J. Biochem. 269 100-109 2002 FEBS 2002 Amphibian peptides that inhibit neuronal nitric oxide synthase The isolation of lesueurin from the skin secretion of the Australian Stony Creek Frog Litoria lesueuri Jason Doyle1 Lyndon E. Llewellyn1 Craig S. Brinkworth2 John H. Bowie2 Kate L. Wegener2 Tomas Rozek2 Paul A. Wabnitz2 John C. Wallace3 and Michael J. Tyler4 1 Australian Institute of Marine Science Townsville MC Queensland Australia 2Departments of Chemistry 3Molecular Biosciences and 4Environmental Biology The University of Adelaide South Australia Two neuropeptides have been isolated and identified from the secretions of the skin glands of the Stony Creek Frog Litoria lesueuri. The first of these the known neuropeptide caerulein is a common constituent of anuran skin secretions and has the sequence pEQY SO3 TGWMDF-NH2. This neuropeptide is smooth muscle active an anal-gaesic more potent than morphine and is also thought to be a hormone. The second neuropeptide a new peptide has been named lesueurin and has the primary structure GLLDILKKVGKVA-NH2. Lesueurin shows no significant antibiotic or anticancer activity but inhibits the formation of the ubiquitious chemical messenger nitric oxide from neuronal nitric oxide synthase nNOS at IC50 M and is the first amphibian peptide reported to show inhibition of nNOS. As a consequence of this activity we have tested other peptides previously isolated from Australian amphibians for nNOS inhibition. There are three groups of peptides that inhibit nNOS IC50 at M concentrations these are a the citropin aurein type peptides of which lesueurin is a member . citropin GLFDVIKKVASVIGGL-NH2 im b the frenatin type peptides . frenatin 3 GLMSVLGHAVGNVLG GLFKPK-OH m and c the caerin 1 peptides . caerin GLFGvLgSIAKHLLPHVVPViAEkL-NH2 M . From Lineweaver-Burk plots the mechanism of inhibition is revealed as noncompetitive with respect to the nNOS substrate arginine. When the nNOS inhibition tests .