Presence Of Vinblastine Research Articles

Difference in effects of vinblastine and vincristine on the dog platelet aggregation.

The present study was attempted to determine difference in effects of vinblastine and vincristine on ADP-induced aggregation of dog platelets. Vinblastine manifested biphasic influence depending upon concentrations, i.e., in low concentrations (0.2-20 micrograms/ml) it promoted the aggregation, and in a high concentration (100 micrograms/ml) it inhibited the aggregation with increasing incubation time. Vincristine in any concentrations, however, neither promoted nor inhibited the aggregation. In scanning electron micrographs, platelets were gradually damaged as revealed by their surface appearances with increasing incubation time in the presence of vinblastine (100 micrograms/ml). There existed a parallel relationship between the inhibition of the aggregation by vinblastine and the increase in number of severely damaged platelets. However, there was no such a parallel relationship between them in the presence of vincristine.

Concanavalin A receptors, immunoglobulins, and theta antigen of the lymphocyte surface. Interactions with concanavalin A and with Cytoplasmic structures.

The effect of concanavalin A (Con A) on the capping of mouse lymphocyte surface immunoglobulin (surface Ig), cross-linked by rabbit anti-mouse Ig antibody, and on the capping of mouse thymocyte theta antigen, cross-linked by anti-theta alloantibody and rabbit anti-mouse Ig antibody, has been studied by immunofluorescence, using fluorescein conjugated Con A and rhodamine-conjugated anti-mouse Ig antibody, and by electron microscopy, using native or fluorescein-conjugated Con A and ferritin-conjugated anti-mouse Ig antibody. Prior incubation of the cells with Con A inhibited only partially capping os surface Ig, whereas it blocked almost completely capping of theta antigens. Both on cells with rings and on cells with caps the staining for surface Ig or theta antigen was superimposed to the staining for Con A. When Con A receptors on spleen cells were capped by Con A at concentrations of 10 mug/ml or higher, and the distribution of surface Ig was examined under noncapping conditions, all detectable surface Ig were found in the caps. As shown by electron microscopy, surface Ig remained dispersed in a layer of Con A. The ability of Con A to cap surface Ig was not altered by the presence of cohchicine or vinblastine. These results suggest that surface Ig are cross-linked by Con A to other Con A receptors. In these conditions surface Ig behave essentially as Con A receptors, as for example, in their sensitivity to cytochalasin B during inhibition or reversal of capping induced by this drug. The behavior of surface Ig parallels that of Con A receptors also in the presence of vinblastine. It is concluded that in the presence of Con A, antimitotic drugs do not modify directly the interaction between Con A receptors and surface Ig, but probably influence the capping ability of the Con A receptors or, more in general, affect the ability to elicit movements over the cell surface. The role in capping of cytochalasin-sensitive and vinblastine-sensitive structures is discussed. Both types of structures appear to play an active role in the formation of a cap, although the former probably corresponds to the main mechanical system responsible for the active displacement of cytoplasmic and surface material.

Microtubules and the Intracellular Conversion of Proparathyroid Hormone to Parathyroid Hormone1

The effects of several compounds which interfere with cellular microfilaments and microtubules on the conversion of proparathyroid hormone (ProPTH) to parathyroid hormone (PTH) were examined in slices of bovine parathyroid slices incubated in vitro with 3H-leucine. Inhibitors of microtubular function, vinblastine and colchicine, increased the ratio of 3H-labeled ProPTH to PTH in the tissue by 2- to 3-fold. Cytochalasin B, an inhibitor of microfilaments, was without effect. Concentrations of colchicine as low as 10-6M maximally increased the ratio of ProPTH to PTH, whereas lumicolchicine, an analogue of colchicine which does not affect the function of microtubules, had no effect at concentrations as high as 10-4M. The increased ratio of ProPTH to PTH was due partly to a stimulation by vinblastine and colchicine of the incorporation of 3H-leucine into ProPTH but not into general protein. However, after short incubations of parathyroid tissue with 3-H-leucine, the amount of 3H-labeled PTH was less in colchine-treated incubations than in control incubations. In the presence of vinblastine, after a 20-min incubation of parathyroid slices with 3H-leucine and vinblastine, ProPTH was not completely converted to PTH by an additional 90-min "chase" incubation with unlabeled leucine while a 20-min "chase" incubations is sufficient to convert essentially all the ProPTH to PTH in control incubations. These data suggest that the increased ratio of ProPTH to PTH is also due to a partial inhibition of the conversion ProPTH to PTH by vinblastine and colchicine. The data are consistent with the hypothesis that microtubules facilitate the transport of newly synthesized ProPTH to its intracellular site of cleavage to PTH.

Fast axonal transport in vitro in the sciatic system of the frog.

Abstract— An in vitro system from the frog has been used to study fast axonal protein transport. The preparation, which was incubated in a specially made chamber, consisted of the gastrocnemius muscle, the sciatic nerve, the dorsal ganglia and part of the spinal cord. The parts were separated from each other by silicone grease barriers, which made it possible to follow the migration of labelled proteins from the spinal cord and ganglia, along the sciatic nerve, towards the muscle. About 80 per cent of transported proteins in the sciatic nerve originated from the dorsal spinal ganglia and moved antidromically at a rate of 60–90 mm per day at 18°C. The rapidly transported proteins were 90 per cent particulate and mainly associated with structures sedimenting in the microsomal fraction.The effects of cyclohexirnide showed that the synthesis of rapidly moving proteins and their transport were separate processes. A low concentration of colchicine inhibited the transport when it was present in the medium surrounding the ganglia, but had no effect even at a higher concentration, when it was added to the nerve compartment. The presence of vinblastine at a low concentration in either of the two compartments completely arrested the protein transport. Likewise N‐ethylmaleimide or p‐chloromercuribenzene sulphonic acid in the nerve medium effectively blocked the fast transport. Results from experiments performed to test the possibility of disto‐proximal flow and of transfer of proteins from the muscle to the nerve are discussed.

Colchicine, vinblastine and griseofulvin: Pharmacological studies with human leukocytes

Some aspects of the interactions of the vinca alkaloids, colchicine and griseofulvin with human leukocytes in suspension have been explored. Tritiated colchicine, vinblastine and griseofulvin enter the cells where significant binding by a supernatant protein takes place. Glutamate competitively inhibits the entry of vinblastine into the leukocytes when present in large excess. Inhibition of the incorporation of valine- 14C into leukocyte protein occurred in the presence of vinblastine and vincristine at concentrations down to 6 × 10 −6 M; colchicine and griseofulvin did not affect this incorporation until levels of 3 × 10 −4 M were attained. Concentrations of these agents as high as 1 × 10 −4 M did not inhibit the incorporation of uridine- 3H NA or of acetate- 14C into lipid. The data were considered to support the concept that the antimitotic and anti-inflammatory effects of vinca alkaloids, colchicine and griseofulvin result from binding to precursor units of the microtubules.