Abstract
The effects of a series of vinca alkaloids on calcium-calmodulin regulated brain cyclic adenosine 3',5'-monophosphate phosphodiesterase (PDE) activity were examined. The alkaloids tested included the dimeric indole alkaloids, vinblastine, vincristine and desacetylvinblastine amide, and the monomeric alkaloids, catharanthine and vindoline. The order of magnitude of the inhibitory effects on the calcium-calmodulin stimulated activity of phosphodiesterase was vinblastine > desacetylvinblastine amide s > vincristine = catharanthine > vindoline. In contrast, both catharanthine and vindoline were more potent inhibitors than the dimeric vinca alkaloids of the basal unstimulated phosphodiesterase activity. Vinblastine and vincristine inhibition of calcium-calmodulin activated partially purified PDE was non-competitive with substrate. In contrast, the inhibitory actions of vinblastine, desacetylvinblastine amide, vincristine and catharanthine, but not of vindoline, were competitive with calcium-calmodulin. Colchicine inhibited both activated and basal phosphodiesterase activity. The inhibitory effect of colchicine was not reversed by the addition of either calmodulin or calcium. These results suggest that the calcium-calmodulin dependent inhibition of PDE activity by the dimeric vinca alkaloids had the greater specificity, and that this inhibitory action required the catharanthine moiety. In view of these results, dimeric vinca alkaloids may provide a useful tool for the elucidation of the physiological role of calcium-calmodulin.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call