Pertwee R G, Fernando S R, Griffin G, Abadji V, Makriyannis A
Department of Biomedical Sciences, Marischal College, University of Aberdeen, Scotland, UK.
Eur J Pharmacol. 1995 Jan 5;272(1):73-8. doi: 10.1016/0014-2999(94)00618-h.
The endogenous cannabinoid receptor ligand, anandamide, produced a concentration related inhibition of electrically evoked contractions of the guinea-pig myenteric plexus preparation. Its potency was markedly enhanced by phenylmethylsulphonyl fluoride (2.0-200 microM) which presumably acts by inhibiting the hydrolysis of anandamide in this preparation. The degree of this potentiation increased with the concentration of phenylmethylsulphonyl fluoride used. The methyl analogue of anandamide, R-(+)-arachidonyl-1'-hydroxy-2'-propylamide, also inhibited contractions of the guinea-pig myenteric plexus preparation. The potency of this 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 inhibitory potency of the cannabinoid, CP 55,940 ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4- [3-hydroxypropyl]cyclohexan-1-ol), which is not an amidase substrate. Nor did phenylmethylsulphonyl fluoride affect the ability of anandamide to inhibit electrically evoked contractions of the mouse vas deferens, suggesting that anandamide does not undergo hydrolysis in this tissue.
内源性大麻素受体配体花生四烯乙醇胺对豚鼠肠肌丛标本的电诱发收缩产生浓度相关的抑制作用。苯甲基磺酰氟（2.0 - 200微摩尔）可显著增强其效力，推测其作用机制是抑制该标本中花生四烯乙醇胺的水解。这种增强程度随所用苯甲基磺酰氟浓度的增加而增大。花生四烯乙醇胺的甲基类似物R-(+)-花生四烯酰-1'-羟基-2'-丙酰胺也能抑制豚鼠肠肌丛标本的收缩。该化合物的效力受苯甲基磺酰氟的影响远小于花生四烯乙醇胺，证实其对水解的抵抗力更强。苯甲基磺酰氟不会改变大麻素CP 55,940（(-)-3-[2-羟基-4-(1,1-二甲基庚基)苯基]-4-[3-羟丙基]环己醇）的抑制效力，CP 55,940不是酰胺酶的底物。苯甲基磺酰氟也不影响花生四烯乙醇胺抑制小鼠输精管电诱发收缩的能力，这表明花生四烯乙醇胺在该组织中不会发生水解。
