THE NOVEL MARINE NATURAL PRODUCT PLOCAMADIENE A CAUSES HISTAMINE RELEASE FROM MAST CELLS OF THE GUINEA-PIG AND RAT IN VITRO |
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Authors: | Steven G. Thomas rew A. Beveridge |
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Affiliation: | Department of Pharmacology, Monash University, Clayton, Victoria, Australia |
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Abstract: | 1. Plocamadiene A is a polyhalogenated monoterpene, (1R, 2S, 4S, 1′E)-2-bromo-l-chloro-4-(2′-chloroethenyl)-I-methyl-5-methylenecyclohexane, isolated from red marine algae of the Plocamium genus. 2. This study examined the activity of plocamadiene A on guinea-pig isolated ileum (GPI) and subsequently on rat isolated peritoneal mast cells. 3. Plocamadiene A (1 μg/mL) produced a slow onset, sustained contraction of the GPI. This was insensitive to atropine (1 μmol/ L) and tetrodotoxin (1 μmol/ L), but was significantly reduced by H1-histamine receptor antagonists including mepyramine (10 nmol/L), chlorcyclizine (10 nmol/L) and diphenhydramine (0.1 μmol/L). The H2-histamine receptor antagonists cimetidine (0.1 μmol/L) and ranitidine (10 nmol/L) potentiated the response to plocamadiene A (1 μg/mL). 4. The amplitude of contraction caused by plocamadiene A (1 μg/mL) gradually decreased when the compound was applied repeatedly to the GPI for 5 min every 10 min for 150 min. 5. Contractions to plocamadiene A (1 μg/mL) were reduced to approximately 66% of the time control in ovalbumin-sensitized GPI challenged with ovalbumin to release endogenous contractile agents. 6. Cromolyn (0.1 mmol/ L) inhibited (by 40%) the response in the GPI caused by plocamadiene A (1 μg/mL) as compared with time controls. 7. Spectrofluorometric assay suggested that both plocamadiene A (10 μg/mL) and compound 48/80 (10 μg/mL) caused histamine release from rat peritoneal mast cells in vitro. This release of histamine was reduced by cromolyn (100 μg/mL). 8. This study concluded that plocamadiene A releases histamine from mast cells of the GPI and peritoneal mast cells in the rat. |
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Keywords: | cromolyn, disodium cromoglycate, histamine, histamine liberation, marine toxins, mast cells, pharmacology, red algae, terpenes. |
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