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INHIBITION BY MORPHINE OF PROSTAGLANDIN E 1 ‐STIMULATED SECRETION AND CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE FORMATION IN THE RAT JEJUNUM in vivo
Author(s) -
BEUBLER E.,
LEMBECK F.
Publication year - 1980
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.1476-5381.1980.tb14566.x
Subject(s) - theophylline , medicine , endocrinology , phosphodiesterase inhibitor , chemistry , adenosine , prostaglandin e , in vivo , jejunum , prostaglandin e2 , morphine , (+) naloxone , prostaglandin e1 , cyclic adenosine monophosphate , prostaglandin , biology , opioid , receptor , microbiology and biotechnology
1 The effects were studied of prostaglandin E 1 (PGE 1 ), theophylline and morphine on net water flux and mucosal cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo . 2 Infusion of PGE 1 (3.2 μg/min, i.a.) caused a reversal from net water absorption to net secretion and enhanced the mucosal cyclic AMP content by 54%. 3 Theophylline (5 mg/ml, intraluminal) similarly produced a reversal from net water absorption to net secretion and increased mucosal cyclic AMP content by 54%. Additional intra‐arterial infusion of PGE 1 resulted in a massive increase in net water secretion and an increase in mucosal cyclic AMP content by about 200%. 4 Pretreatment with morphine (10 mg/kg, s.c.) reduced the effect of PGE 1 on net water flux and completely inhibited its effect on the mucosal cyclic AMP content. Naloxone (10 mg/kg, s.c.) abolished both effects of morphine. 5 A good correlation ( r = 0.99) was demonstrated between mucosal cyclic AMP levels and net water flux. 6 The present results demonstrate that PGE 1 stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels. The antidiarrhoeal effect of morphine can be explained by its inhibition of the PGE‐mediated increase in cyclic AMP levels, which, in turn, leads to a reduction in intestinal secretion.