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

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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 Ca(2+)-activated K+ channels (apamine, etc.) have been studied extensively by numerous investigators. Peptide toxins, calciseptine and omega-conotoxins have been attracting much attention as inhibitors of L-type and N-type Ca2+ channels, respectively, while omega-conotoxins-MVIIC and omega-agatoxin IVA have been used as new types of Ca(2+)-channel blockers. Ryanodine and bromoeudistomin D analogues have been extensively used to elucidate Ca(2+)-release-channel functions and to purify its target protein. Polypeptide toxins (myotoxin alpha, 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 Ca(2+)-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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