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Paul SM, Halaris AE, Freedman DX, Hau LL.
“Rat brain aryl acylamidase: stereospecific inhibition by LSD and serotonin-related compounds”.
J. Neurochem.. 1976;27:625-627.
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Abstract
ENZYMATIC de-acetylation of acylamides by both mammalian tissues and plants has been studied for many years (KREBS et al:, 1947: NIMMO-SM;TH, 1960). A number of investigators have reported significant hydrolysis of these N-acetylated compounds to their corresponding aryl amines by brain tissue in vitro (BRAY et al., 1949; HOAG LAND GRAF, 1971), but, to our knowledge, this enzymatic activity has neither been characterized nor its existence firmly established. Our investigation of rat brain de-acetylating activity (aryl acylamidase, EC 3.5.1.13) was prompted by recent reports of significant N-acetylating activity within dialysed brain extracts (YANG NEFF, 1974; PAUL et al., 1974), as well as the demonstration in brain of N-acetylated metab olites of such aromatic amines as serotonin, 5-methoxy - tryptamine, and mescaline (KOSLOW, 1 974; SEILER & DEMISCH, 1974). During the course of our studies on the N-acetyltransferase activity of rat brain, a brief report describing a serotonin-sensitive de-acetylase in rat brain was published (FunMoro, 1974). The presence in rat brain of de-acetylating activity that is inhibited by low concen - trations of at least one potential substrate for the N-acetyl ating activity (i.e. serotonin), warranted further investiga - tion Our initial studies revealed-a significant heterogeneity within the total de-acetylating activity of rat.brain; the enzymatic activity of rat brain displayed at least two dis - tinct pH optima and-following column chromatography multiple activity peaks were observed (Hsu et al., In press) However, we confirmed that at least a.portion of this acti vity was inhibited by low concentrations of serotonin, as had been previously reported (FWIMOTO, 1974). This study was undertaken to examine the specificity of this inhibition by studying the effects of closely related tryptamine deriva tives. Our results demonstrate that the inhibition of rat brain aryl acylamidase occurs only in the presence of phar macologically active tryptamine derivatives, is stereospeci tic with respect to its inhibition by lysergic acid diethyl amide (LSD), and thus might provide a basis for studying LSD serotonin-receptor interaction in vitro.
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