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PHARMACOLOGICAL PROPERTIES OF THE NATURAL MARINE PRODUCT FUROSPONGIN‐1
Author(s) -
Anderson Andrew P.,
Beveridge Andrew A.,
Capon Robert
Publication year - 1994
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.1440-1681.1994.tb02656.x
Subject(s) - oligomycin , mepyramine , acetylcholine , histamine , phentolamine , chemistry , endocrinology , medicine , atropine , contraction (grammar) , ileum , biology , biochemistry , antagonist , stimulation , atpase , receptor , enzyme
SUMMARY 1. The natural marine product, furospongin‐1 (6, 12 and 24.5 μmol/L) significantly inhibited contractions of segments of guinea‐pig ileum induced by submaximal concentrations (0.1 μmol/L) of acetylcholine (ACh) and histamine. Furospongin‐1 (24.5 and 36.7 μmol/L) 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 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/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 μmol/ 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 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/L). 3. Furospongin‐l (6 and 37.6 μmol/L) and oligomycin (3 μmol/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 μmol/L) and oligomycin (0.3, 1 and 3 μmol/L) concentration‐dependently reduced tissue levels of ATP. 4. In lyzed bovine mitochondria, oligomycin (0.1, 0.3, 1 and 3 μmol/L) inhibited conversion of ATP to ADP whilst furospongin‐1 (6, 12 and 24.5 μmol/L) and carbonyl cyanide m ‐chlorophenylhydrazone (0.5 mmol/L) had no significant effect on ATP breakdown. 5. Furospongin‐1 (12 and 24.5 μmol/L) and oligomycin (3 μmol/L) had no effect on State 4 mitochondrial respiration of whole bovine mitochondria, but converted State 3 back to State 4 respiration. Carbonyl cyanide m ‐chlorophenyl‐hydrazone (0.5 mmol/L) increased oxygen consumption in both situations. 6. These results suggest that furospongin‐1 may inhibit the activity of inner mitochondrial membrane ADP‐ATP translocases or other membrane transporters to inhibit ATP synthesis.