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The inhibition of CYP enzymes in mouse and human liver by pilocarpine
Author(s) -
Kimonen Tanja,
Juvonen Risto O.,
Alhava Esko,
Pasanen Markku
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13279.x
Subject(s) - microsome , pilocarpine , cyp3a , cytochrome p450 , cyp2a6 , chemistry , microsoma , medicine , isozyme , enzyme , endocrinology , testosterone (patch) , biochemistry , biology , cyp1a2 , neuroscience , epilepsy
1 Pilocarpine is a cholinomimetic natural alkaloid. Its interactions with testosterone hydroxylations, coumarin 7‐hydroxylase (COH), dimethylnitrosamine N‐demethylase (DMNA), pentoxyresorufin O‐dealkylase (PROD) and 7‐ethoxyresorufin O‐deethylase (EROD), which are indicative of the activities of cytochrome P4502A5 (CYP2A5) or 6, 2E1, 2B, 1A, were examined in mouse and human liver microsomes. 2 In mouse liver microsomes the IC 50 values of pilocarpine were 6 μ m for COH and testosterone 15a‐hydroxylase (T15αOH) activities, 4 μ m for PROD, ≅ 100 μ m for DMNA and testosterone 60‐hydroxylase (T6βOH) activities and > 1 m m for EROD activity. 3 In human liver microsomes, the IC 50 value for COH was 6 μ m and for DMNA 10 μ m ; T15αOH and PROD activities were not detectable but T6βOH and testosterone 16β/2β‐hydroxylase activities were moderately inhibited (IC 50 70 μ m ). 4 These results suggest that pilocarpine has (i) a high affinity towards phenobarbitone‐inducible CYP2A4/5 and CYP2B activities in mouse liver, (ii) a high affinity towards CYP2A6 in human liver microsomes and (iii) a moderate affinity towards CYP3A enzyme(s) in both microsomal preparations. 5 The low IC 50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes.