The novel marine natural product plocamadiene A causes histamine release from mast cells of the guinea-pig and rat in vitro.
1. Plocamadiene A is a polyhalogenated monoterpene, (1R, 2S, 4S, 1'E)-2-bromo-1-chloro-4-(2'-chloroethenyl)-1-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 micrograms/mL) produced a slow onset, sustained contraction of the GPI. This was insensitive to atropine (1 mumol/L) and tetrodotoxin (1 mumol/L), but was significantly reduced by H1-histamine receptor antagonists including mepyramine (10 nmol/L), chlorcyclizine (10 nmol/L) and diphenhydramine (0.1 mumol/L). The H2-histamine receptor antagonists cimetidine (0.1 mumol/L) and ranitidine (10 nmol/L) potentiated the response to plocamadiene A (1 micrograms/mL). 4. The amplitude of contraction caused by plocamadiene A (1 micrograms/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 micrograms/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 micrograms/mL) as compared with time controls. 7. Spectrofluorometric assay suggested that both plocamadiene A (10 micrograms/mL) and compound 48/80 (10 micrograms/mL) caused histamine release from rat peritoneal mast cells in vitro. This release of histamine was reduced by cromolyn (100 micrograms/mL). 8. This study concluded that plocamadiene A releases histamine from mast cells of the GPI and peritoneal mast cells in the rat.
Thomas
S G
SG
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Beveridge
A A
AA
D000818:Animals; D002478:Cells, Cultured; D004205:Cromolyn Sodium / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013729:Terpenes / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D008387:Marine Toxins; D013729:Terpenes; C028092:plocamadiene A; D010047:Ovalbumin; D004205:Cromolyn Sodium