Application of Physiologically Active Substances Isolated from Natural Resources to Pharmacological Studies.

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  • Ohizumi Yasushi
    Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University

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  • Application of Physiologically Active S

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Abstract

Numerous neurotoxins that alter Na+-channel function have been shown to be useful tools for characterizing Na+ channels. Polypeptide blockers of voltage-dependent K+ channels (dendrotoxins, etc.) and Ca2+ -activated K+ channels (apamine, etc.) have been studied extensively by numerous investigators. Peptide toxins, calciseptine and ω-conotoxins have been attracting much attention as inhibitors of L-type and N-type Ca2+ channels, respectively, while ω-conotoxins-MVIIC and ω-agatoxin IVA have been used as new types of Ca2+ -channel blockers. Ryanodine and bromoeudistomin D analogues have been extensively used to elucidate Ca2+ -release-channel functions and to purify its target protein. Polypeptide toxins (myotoxin α, etc.) and macrolides (FK 506, etc.) are useful Ca2+ releasers with a novel mechanism, while natural products such as thapsigargin and gingerol have been used as modulators of Ca2+ -pumping ATPase. Some modulators of the function of myosin (purealin, etc.) and actin (goniodomin A, etc.)have been demonstrated to be important chemical probes for understanding the physiological roles of the contractile proteins in structural changes and their interaction in muscle contraction. A large number of protein kinase inhibitors (staurosporine, etc.) and phosphatase inhibitors (okadaic acid, etc.)are widely used as first-choice reagents for studying protein phosphorylation. These natural products have become essential tools for studying the regulatory mechanism of cellular ion movements, muscle contraction and protein phosphorylation.

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