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INDOMETHACIN‐INDUCED INCREASE IN NORADRENALINE TURNOVER IN SOME RAT ORGANS
Author(s) -
FREDHOLM B.B.,
HEDQVIST P.
Publication year - 1975
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.1476-5381.1975.tb07568.x
Subject(s) - endocrinology , medicine , monoamine oxidase , adipose tissue , chemistry , turnover , prostaglandin , spleen , norepinephrine , kidney , submandibular gland , biology , dopamine , biochemistry , enzyme , management , economics
1 The effect of a prostaglandin synthesis inhibitor, indomethacin, on noradrenaline turnover rate in various rat tissues was determined from the product of the endogenous noradrenaline concentration and of the rate constant of (—)‐[ 3 H]‐noradrenaline decline after injection of the labelled amine in tracer doses. 2 Treatment of the rats with indomethacin (5 mg/kg p.o. five times during 2.5 days) increased noradrenaline turnover rate 32–36% in submandibular gland, spleen and heart, and 4–17% in epididymal and subcutaneous adipose tissue. 3 The extrapolated [ 3 H]‐noradrenaline content at time 0 was greater in heart and adipose tissue of indomethacin‐treated animals than in controls, while it was not significantly changed in spleen and salivary gland. 4 There was no apparent relationship between tissue concentrations of intravenously injected [ 14 C]‐indomethacin and the effect of indomethacin on noradrenaline uptake and turnover rate in the different tissues. 5 Indomethacin treatment did not affect monoamine oxidase and catechol O ‐methyl‐transferase activities in the different tissues. 6 The results are consistent with the hypothesis that indomethacin increases noradrenaline turnover in the rat by blockade of a locally operating feed back inhibition of transmitter release by prostaglandins. However, additional effects, such as an increased impulse traffic, cannot be ruled out.