The marine natural product 3,5-dibromo-2-(2,4-dibromo-phenoxy)phenol, inhibits contractile activity in the guinea-pig ileum.
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 mumol/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 mumol/L or greater. 4. BPE (2 mumol/L) did not affect calcium-induced contractions of longitudinal muscle fibres from guinea-pig ileum which were stripped of their cellular membrane. It (6 mumol/L) also had no effect on ATP levels in longitudinal muscle fibres. 5. BPE (2 mumol/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 mumol/L) reduced carbachol-induced contractions of ileum pre-incubated in 1 mumol/L felodipine, a blocker of L-type voltage-operated calcium channels (VOCC). 7. BPE dose dependently (0.6-6 mumol/L) reduced contractions induced by Ca2+ in both K+ depolarized ileum and in tissue exposed to carbachol (10 mumol/L) in the presence of felodipine (0.1 mumol/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).
Bussau
L J
LJ
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Beveridge
A A
AA
Nadeson
R
R
Anderson
A P
AP
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004558:Electric Stimulation; D006168:Guinea Pigs; D055768:Halogenated Diphenyl Ethers; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D015220:Calcium Channels; D055768:Halogenated Diphenyl Ethers; D010636:Phenols; D010647:Phenyl Ethers; D001464:Barium; D012701:Serotonin; C085794:3,5-dibromo-2-(2,4-dibromophenoxy)phenol; D006632:Histamine; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium