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Effect of Δ 9 ‐tetrahydrocannabinol and merthiolate on acyltransferase activities in guinea pig liver microsomesand merthiolate on acyltransferase activities in guinea pig liver microsomes
Author(s) -
Badiani Ketan,
Lu Xiaoli,
Arthur Gilbert
Publication year - 1993
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536314
Subject(s) - guinea pig , lipidology , microsome , delta 9 tetrahydrocannabinol , clinical chemistry , acyltransferase , tetrahydrocannabinol , pharmacology , biology , medicine , chemistry , endocrinology , biochemistry , enzyme , cannabinoid , receptor
Δ 9 ‐tetrahydrocannabinol (THC) and merthiolate have been utilized as lysophospholipid acyltransferase inhibitors in metabolic studies. However, their effects on acyltransferases other than lysophosphatidylcholine:acyl‐CoA acyltransferase (LPCAT) are not known. We have therefore investigated the effectiveness of THC and merthiolate in inhibiting the acylation of lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol (LPI) and lysophosphatidic acid (LPA) in guinea pig liver microsomes using oleoyl‐CoA and arachidonoyl‐CoA as acyl donors. THC inhibited LPCAT and lysophosphatidylethanolamine: acyl‐CoA acyltransferase (LPEAT) by 40–50%, but had no effect or only slightly increased the activities of the other acyltransferases when assayed with oleoyl‐CoA as the acyl donor. The results obtained with arachidonoyl‐CoA were similar to those with oleoyl‐CoA, with the exception of a 40% inhibition of lysophosphatidylserine:acyl‐CoA acyltransferase (LPSAT) at concentrations of 50 μM or higher. At similar concentrations, merthiolate was more effective than THC in inhibiting the acyltransferases examined. Selective effects on the acyltransferases were observed at low concentrations of merthiolate (20 μM or less). Thus, LPCAT was most susceptible, followed by LPI acyltransferases, LPSAT, LPEAT and lysophosphatidic acid:acyl‐CoA acyltransferases (LPAAT). The presence of LPA did not affect the inhibition of LPCAT by merthiolate. Thus the resilience of LPAAT to merthiolate inhibition was not due to chelation of the compound by the acidic lysolipid. Thiol reagents including N ‐ethylmaleiamide, 5,5′‐dithio‐ bis ‐nitrobenzoic acid, iodoacetate, β‐mercaptoethanol and dithiothreitol had little or no effect on the acyltransferases relative to equimolar concentrations of merthiolate. The above results indicate that merthiolate is a much more effective inhibitor of lysophospholipid:acyl‐CoA acyltransferases than is THC, and that the selectivity exhibited by merthiolate may be due to direct and specific interaction with the acyltransferases.