The pro-inflammatory
tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and
12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 microgram induced
erythema in the mouse ear. Observations of ear redness were made both two and four hours after application.
Indomethacin was only partly successful as an antagonist since 10% inhibition of
12-DOPPA and no inhibition of
12-DOPPAA induced
erythema was produced four hours after application. The
free radical scavengers,
phenol,
thioanisole and
sodium benzoate all produced less than 30% inhibition of
12-DOPPA induced
erythema and less than 15% inhibition of
12-DOPPAA, whereas
aminopyrine produced 70% and 25% inhibition of
12-DOPPA and
12-DOPPAA respectively. The fact that
free radical scavengers (with the exception of
aminopyrine) and
indomethacin, failed to markedly change the mouse ear reaction to 12-deoxyphorbol
esters, indicated that this
erythema is not entirely mediated via
cyclooxygenase products.
Mepyramine and
cyproheptadine also failed to inhibit the
erythema, whereas
hydrocortisone produced a 55% inhibition of the
12-DOPPA and a 20% inhibition of the
12-DOPPAA reaction. The membrane stabilising agents
trifluoperazine,
promethazine,
imipramine and
desmethylimipramine were the most successful compounds used in inhibiting both
12-DOPPA and
12-DOPPAA induced
erythema. In addition
propranolol, which inhibits stimulus activation of
phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to
12-DOPPA and
12-DOPPAA.