EFFECT OF PHENYLMETHYLSULFONYL FLUORIDE ON THE POTENCY OF ANANDAMIDE AS AN INHIBITOR OF ELECTRICALLY-EVOKED CONTRACTIONS IN 2 ISOLATED TISSUE PREPARATIONS

The endogenous cannabinoid receptor ligand, anandamide, produced a con centration related inhibition of electrically evoked contractions of t he guinea-pig myenteric plexus preparation. Its potency was markedly e nhanced by phenylmethylsulphonyl fluoride (2.0-200 mu M) which presuma bly acts by inhibiting the hydrolysis of anandamide in this preparatio n. The degree of this potentiation increased with the concentration of phenylmethylsulphonyl fluoride used. The methyl analogue of anandamid e, R-(+)-arachidonyl-l'-hydroxy-2'-propylamide, also inhibited contrac tions of the guinea-pig myenteric plexus preparation. The potency of t his compound was much less affected by phenylmethylsulphonyl fluoride than was the potency of anandamide, confirming its greater resistance to hydrolysis. Phenylmethylsulphonyl fluoride did not alter the inhibi tory potency of the cannabinoid, CP 55,940 eptyl)phenyl]-4-[3-hydroxyp ropyl]cyclohexan-1-ol), which is not an amidase substrate. Nor did phe nylmethylsulphonyl fluoride affect the ability of anandamide to inhibi t electrically evoked contractions of the mouse vas deferens, suggesti ng that anandamide does not undergo hydrolysis in this tissue.