|Budget Amount *help
¥7,800,000 (Direct Cost : ¥7,800,000)
Fiscal Year 1993 : ¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1992 : ¥4,900,000 (Direct Cost : ¥4,900,000)
PAF(platelet activating factor, 1-0-alkyl-2(R)-(acetylglyceryl)-3-phosphorylcholine) causea platelet aggregation, chemotaxis, and degranulation of polymorphonuclear leukocytes, smooth muscle contraction, m vascular permeability, and hyupotension. Recent studies have shown that PAF may be involved in many inflammator, respiratory, and cardiovascular diseases.
In our project of search for new PAF autagonists from marine organisms, we systematically screened lipophilic extracts of Okinawan marine invertebrates and microorganisms for inhibition of PAF production due to A23817 and inhibition of PAF-induced platelet aggregation to find that several sponge metabolites such as manoalide, luffariolide A, bistheonllide A, swinholide A, niphatesine A, and heteronemin, exhibited PAF antagonistic activities with IC_<50> values of 0.05 - 5.0 mu g /mL.More powerful and specific PAF antagonistis may be fond through further studies of structure-activity relationship on the compounds (terpenes, alkaloid, etc.) described above.