Pharmacological properties of the natural marine product furospongin-1.
1. The natural marine product, furospongin-1 (6, 12 and 24.5 mumol/L) significantly inhibited contractions of segments of guinea-pig ileum induced by submaximal concentrations (0.1 mumol/L) of acetylcholine (ACh) and histamine. Furospongin-1 (24.5 and 36.7 mumol/L) reduced both the phasic and tonic components of a contraction induced by 30 mumol/L K+ solution in the absence and presence of atropine (1 mumol/L), mepyramine (1 mumol/L) and phentolamine (1 mumol/L). Furospongin-1 also decreased basal tension and the amplitude of spontaneous phasic contractions of guinea-pig ileum. 2. The mitochondrial ATP synthase inhibitor oligomycin (0.3, 1 and 3 mumol/L) had a similar concentration-dependent action, reducing basal activity and contractions evoked by histamine and ACh. Oligomycin also reduced both the phasic and tonic components of a contraction induced by 30 mmol/L K+ solution in the absence and presence of atropine (1 mumol/L), mepyramine (1 mumol/L) and phentolamine (1 mumol/L). 3. Furospongin-1 (6 and 37.6 mumol/L) and oligomycin (3 mumol/L) had no effect on contractions of chemically skinned guinea-pig ileum longitudinal muscle segments. In this same tissue, furospongin-1 (6, 12 and 24.5 mumol/L) and oligomycin (0.3, 1 and 3 mumol/L) concentration-dependently reduced tissue levels of ATP. 4. In lyzed bovine mitochondria, oligomycin (0.1, 0.3, 1 and 3 mumol/L) inhibited conversion of ATP to ADP whilst furospongin-1 (6, 12 and 24.5 mumol/L) and carbonyl cyanide m-chlorophenylhydrazone (0.5 mmol/L) had no significant effect on ATP breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
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AP
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Beveridge
A A
AA
Capon
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism
D005663:Furans; D008387:Marine Toxins; C093369:furospongin 1; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D011188:Potassium