M. Robinson et al., INHIBITION OF PHORBOL ESTER-STIMULATED ARACHIDONIC-ACID RELEASE BY ALKYLGLYCEROLS, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1254(3), 1995, pp. 361-367
Although synthetic analogs of alkylglycerol (AG), such as dodecylglyce
rol, possess potent biological activities, their mechanism of action h
as not been determined. We recently detected substantial amounts of AG
in unstimulated MDCK cells (Warne, T.R. and Robinson, M. (1991) Anal.
Biochem. 198, 302-307) raising the possibility that the endogenous co
mpound may act as a biological mediator. In this study, we examined th
e effects of synthetic AG on the release elf arachidonic acid and arac
hidonate metabolites (AA) from Madin Darby canine kidney (MDCK) cells
in response to 12-O-tetradecanylphorbol-13-acetate (TPA) in order to c
haracterize its effects on this signalling pathway. Treatment of MDCK
with AG potently inhibited the release of AA during subsequent stimula
tion with TPA. Dodecylglycerol, the most effective of a series of alky
glycerols tested, was active at concentrations as low as 3 mu M. The s
n-1 and sn-3 forms of AG were found to be equally potent inhibitors. T
he effects of AG on AA release were not the result of arachidonic acid
redistribution among cellular lipids and were independent of the phos
pholipid source of the released AA. AG did not inhibit the release of
AA from MDCK cells when bradykinin was used as a stimulus, indicating
selectivity for the effects produced by phorbol esters. These results
show that AG can function as a potent and specific inhibitor of TPA-me
diated AA release. The ability of AG to regulate this signalling pathw
ay in intact MDCK cells, together with its natural occurrence, suggest
s a potential bioregulatory role for the endogenous compound as an inh
ibitor of protein kinase C.