PMID- 11818382
OWN - NLM
STAT- MEDLINE
DCOM- 20020214
LR  - 20181130
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 43
IP  - 2
DP  - 2002 Feb
TI  - Effect of the enzyme inhibitor, phenylmethylsulfonyl fluoride, on the IOP 
      profiles of topical anandamides.
PG  - 393-7
AB  - 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 antagonist SR141716A. METHODS: AEA or APN were 
      each formulated in aqueous 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) 
      solutions and administered unilaterally to the rabbit eye (dose, 62.5 microg 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 receptor.
FAU - Laine, Krista
AU  - Laine K
AD  - Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland. 
      krista.laine@uku.fi
FAU - Jarvinen, Kristiina
AU  - Jarvinen K
FAU - Pate, David W
AU  - Pate DW
FAU - Urtti, Arto
AU  - Urtti A
FAU - Jarvinen, Tomi
AU  - Jarvinen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Arachidonic Acids)
RN  - 0 (Cannabinoids)
RN  - 0 (Endocannabinoids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Piperidines)
RN  - 0 (Polyunsaturated Alkamides)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Cannabinoid)
RN  - 0 (Receptors, Drug)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 57KD15003I (Phenylmethylsulfonyl Fluoride)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.- (fatty-acid amide hydrolase)
RN  - RML78EN3XE (Rimonabant)
RN  - UR5G69TJKH (anandamide)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Administration, Topical
MH  - Amidohydrolases/*antagonists & inhibitors
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Arachidonic Acids/*administration & dosage
MH  - Cannabinoids/*administration & dosage
MH  - Endocannabinoids
MH  - Enzyme Inhibitors/*pharmacology
MH  - Female
MH  - Indomethacin/administration & dosage
MH  - Intraocular Pressure/*drug effects
MH  - Male
MH  - Ophthalmic Solutions
MH  - Phenylmethylsulfonyl Fluoride/*pharmacology
MH  - Piperidines/administration & dosage
MH  - Polyunsaturated Alkamides
MH  - Pyrazoles/administration & dosage
MH  - Rabbits
MH  - Receptors, Cannabinoid
MH  - Receptors, Drug/antagonists & inhibitors/metabolism
MH  - Rimonabant
EDAT- 2002/01/31 10:00
MHDA- 2002/02/15 10:01
CRDT- 2002/01/31 10:00
PHST- 2002/01/31 10:00 [pubmed]
PHST- 2002/02/15 10:01 [medline]
PHST- 2002/01/31 10:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2002 Feb;43(2):393-7.