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THE MARINE NATURAL PRODUCT 3,5‐DIBROMO‐2‐(2,4‐DIBROMO‐PHENOXY)PHENOL, INHIBITS CONTRACTILE ACTIVITY IN THE GUINEA‐PIG ILEUM
Author(s) -
Bussau Lindsay J.,
Beveridge Andrew A.,
Nadeson Ray,
Anderson Andrew P.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01654.x
Subject(s) - ileum , carbachol , endocrinology , medicine , chemistry , acetylcholine , calcium , histamine , muscle contraction , stimulation , biology
SUMMARY 1. The tetrabrominated diphenyl ether 3,5‐dibromo‐2‐(2,4‐dibromophenoxy)phenol (BPE), a natural marine product isolated from a sponge, was tested for pharmacological activity in guinea‐pig ileum. 2. BPE (2 μmol/ L) decreased basal force and the frequency of spontaneous contractions of the ileum. It also significantly decreased contractions of the ileum induced by 5 mmol/L barium and to electrical stimulation at parameters which stimulated intrinsic nerves. 3. The slopes of concentration‐response curves to acetylcholine (ACh), histamine and 5‐hydroxytryptamine (5‐HT) were significantly reduced by BPE at concentrations of 2 μmol/L or greater. 4. BPE (2 μmol/L) did not affect calcium‐induced contractions of longitudinal muscle fibres from guinea‐pig ileum which were stripped of their cellular membrane. It (6 μmol/L) also had no effect on ATP levels in longitudinal muscle fibres. 5. BPE (2 μmol/L) reduced both phasic and tonic components of contractions induced by raising the extracellular concentration of K + to 15, 30, 45 or 60 mmol/ L (in the presence of atropine, propranolol, phentolamine and desensitization to 5‐HT to inhibit the effects of nerve transmitter release). 6. BPE (2 μmol/L) reduced carbachol‐induced contractions of ileum pre‐incubated in 1 μmol/L felodipine, a blocker of l‐type voltage‐operated calcium channels (VOCC). 7. BPE dose dependently (0.6–6 μmol/L) reduced contractions induced by Ca 2+ in both K + depolarized ileum and in tissue exposed to carbachol (10 μmol/L) in the presence of felodipine (0.1 μmol/L). 8. These results suggest that BPE affects intracellular messenger systems controlling cytosolic calcium and/or blocks entry of calcium into the cell through both VOCC and receptor‐operated channels (ROC).