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Krista Laine, Kristiina Järvinen, David W. Pate, Arto Urtti, Tomi Järvinen; Effect of the Enzyme Inhibitor, Phenylmethylsulfonyl Fluoride, on the IOP Profiles of Topical Anandamides. Invest. Ophthalmol. Vis. Sci. 2002;43(2):393-397.
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purpose. Earlier studies have suggested that the intraocular pressure (IOP)
effects of topical arachidonylethanolamide (AEA) are mediated through
its fatty acid metabolite, rather than through AEA, per se. The purpose
of this study was to investigate whether the topical anandamides AEA
and arachidonyl propionitrileamide (APN) decrease IOP when their
enzymatic degradation is prevented by phenylmethylsulfonyl fluoride
(PMSF) and whether the neuronal cannabinoid (CB1) receptor mediates the
IOP responses of an undegraded AEA, through the use of its specific
methods. AEA or APN were each formulated in aqueous
2-hydroxypropyl-β-cyclodextrin (HP-β-CD) solutions and administered
unilaterally to the rabbit eye (dose, 62.5 μg per rabbit). To prevent
the degradation of AEA or APN, the rabbits were pretreated with a
subcutaneous (SC) PMSF injection (0.22–22 mg/kg) 30 minutes before eye
drop instillation. To determine whether the neuronal cannabinoid (CB1)
receptor mediates the hypotensive IOP effects of undegraded AEA, the
rabbits were pretreated with simultaneous SC injections of a CB1
receptor antagonist SR141716A (1.2–2.1 mg/kg) and PMSF (2.2 mg/kg)
before the ocularly applied AEA.
results. In the absence of PMSF, the IOP profiles of AEA and APN showed a
biphasic ocular effect—that is, an initial increase of IOP followed by
IOP hypotension in the treated eye. In the presence of PMSF (2.2 mg/kg
for AEA and 22 mg/kg for APN), IOP profiles showed immediate IOP
reduction in the treated eye. SR141716A antagonized the IOP reduction
caused by the undegraded AEA.
conclusions. These results indicate that the apparently undegraded AEA and APN
decrease IOP in normotensive rabbits. AEA-induced IOP reduction in the
presence of PMSF is probably mediated through a CB1
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