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THE NOVEL MARINE NATURAL PRODUCT PLOCAMADIENE A CAUSES HISTAMINE RELEASE FROM MAST CELLS OF THE GUINEA‐PIG AND RAT IN VITRO
Author(s) -
Thomas Steven G.,
Beveridge Andrew A.
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.tb01674.x
Subject(s) - histamine , mepyramine , cimetidine , histaminergic , chemistry , guinea pig , ovalbumin , pharmacology , atropine , mast cell , histamine h1 receptor , compound 48/80 , diphenhydramine , endocrinology , receptor , biology , antagonist , biochemistry , degranulation , immunology , immune system
SUMMARY 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 H 1 ‐histamine receptor antagonists including mepyramine (10 nmol/L), chlorcyclizine (10 nmol/L) and diphenhydramine (0.1 μmol/L). The H 2 ‐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.