Phospholipase A2, inhibition

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

There are only a few reports on the efficacy of feverfew in an in vivo situation. Inhibition of collagen-induced bronchoconstriction in an in vivo guinea-pig model was demonstrated [56] and it was concluded that this was consistent with in vivo phospholipase A2 inhibition. In a rat model of experimentally induced nephrocalcinosis, parthenolide was shown to protect the rats against this condition. Inhibition of prostaglandin biosynthesis may have been the mechanism of action of parthenolide in this case, as prostaglandins are thought to be involved in nephrocalcinosis [57]. 

Cheung AK, Murelli R, Snapper ML (2004) Total syntheses of (+)- and (—)-cacospongiono-lide B, cacospongionolide E, and related analogues. Preliminary study of structural features required for phospholipase A2 inhibition. J Org Chem 69 5712-5719... 

Fenard, D., Lambeau, G., Maurin, T., Lefebvre, J. C., and Doglio, A. (2001). A peptide derived from bee venom-secreted phospholipase A2 inhibits replication of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor. Mol. Pharmacol. 60, 341-347. 

Elmore MA, Carrier MJ, Daniels RH, Hill ME, Finnen MJ. Antisense to secretory type II phospholipase A2 inhibits fMLP-in-duced arachidonic acid release in differentiated HL60 s. Biochemical Society Transactions 1994 22-.SI36. 

Murelli, R.P., Cheung, A.K., and Snapper, M.L. (2007) Conforma-tionally restricted (+)-cacospongionolide B analogues. Influence on secretory phospholipase A2 inhibition. J. Org. Chem., 72,1545-1552. 

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