AIMTo investigate the effects of 323-A and 323-B, two isomers extracted from the metabolites of cultured marine fungus, Halorosellinia oceanicum 323, on the contraction of isolated guinea pig ileum (GPI).

METHODSThe GPI contractions were recorded with a two-channel-physiological recorder with tension transducers. Cumulative dose-response curves of contractions of isolated GPI induced by histamine (Hist), acetylcholine (ACh) and potassium chloride (KCl) were constructed, then the influences of 323-A and 323-B on each curve were observed. Furthermore, possible mechanisms underlying effects of the two compounds were explored by analyzing their influences on the biphasic contractile response to ACh, with comparison of a calcium antagonist, verapamil (Ver).

RESULTSThe data indicated that both 323-A and 323-B inhibited the contractile actions of GPI triggered by Hist, ACh and KCl in a concentration-dependent manner, with pD2' values of 5.13, 4.97, 5.36 and 5.51, 5.56, 5.62, respectively. The initial phase component of the ACh-elicited contractions, in the absence of external Ca2+, was significantly reduced by 323-A, 323-B, as well as Ver, whereas the subsequent sustained tonic contractions induced by adding Ca2+ to the bath solution were almost unaffected.

CONCLUSIONThese results suggest that 323-A and 323-B have calcium antagonistic effects similar to that of Ver in mechanisms, and they might have potential to be developed as calcium antagonists.