RT Journal Article
SR Electronic
T1 Non-Cyclic AMP-Dependent, Positive Inotropic Cyclodepsipeptides with Negative Chronotropy
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1006
OP 1012
VO 290
IS 3
A1 Tsunoo, Akinobu
A1 Kamijo, Masayuki
YR 1999
UL http://jpet.aspetjournals.org/content/290/3/1006.abstract
AB The effects of natural cyclodepsipeptides (CDPs) on isolated rat cardiac tissue preparations were examined in vitro. Destruxin A, destruxin B (DB), roseotoxin B (RB), and roseocardin (RC), a novel CDP, each caused a concentration-dependent increase in the contraction force of the right atrium and the papillary and trabecular muscles of the right ventricle at 0.6 to 600 μM. RB, destruxin A, and DB did not affect the half-decay time of relaxation of the papillary muscles, but RC slightly prolonged it, although to a much lesser extent than BA 41899, a calcium sensitizer. This inotropic effect is accompanied by a prolongation of the automatic atrial contraction intervals. The RB-induced increase in the contraction force of papillary muscle was not affected by phentolamine, propranolol, pyrilamine, or cimetidine. RB- and RC-induced increases in the contraction force of papillary muscles were not affected by 3-isobutyl-1-methylxanthine or carbachol. Neither peptide changed the cyclic AMP levels in trabecular muscles. Neither RB nor RC affected the activity of Na+,K+-ATPase from rat kidney. Neither RB, RC, nor DB affected the resting membrane potential or the apparent input resistance of papillary muscles. These results suggest that these CDPs produce both non-cyclic AMP-dependent positive inotropic and negative chronotropic effects. The American Society for Pharmacology and Experimental Therapeutics