Colchicine Alters the Nerve Birefringence Response

Landowne, David; Larsen, James B.; Taylor, Kevin T.

doi:10.1126/science.6302838

Cited by 14 publications

(10 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the large (2.5-to 5.0-fold) enhancement by these agents, cytochalasin B, a microfilamentdisrupting agent, increased the PGE1-induced cAMP levels by only 24 and 63% at 10 and 40 ,AM, respectively (Table 1).…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies concerning the role of microtubules in various cellu-lar reactions have involved the use of agents such as colchicine which, while known to disrupt microtubules, also appear to have actions unrelated to their tubulin-binding property (21)(22)(23)(24). Taxol, in contrast to colchicine, promotes microtubule polymerization and thus may specifically prevent the microtubule-disrupting activity of colchicine.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function.

Wolberg¹,

Stopford²,

Zimmerman³

1984

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Several microtubule-disrupting agents (colchicine, demecolcine, vinblastine, vincristine, podophyllotoxin, and nocodazole) have been shown to inhibit lymphocytemediated cytolysis. These agents also enhanced the prostaglandin El-induced rise in cAMP levels in these cytolytic lymphocytes. Taxol, a natural product alkaloid that has been shown to enhance microtubule polymerization and to stabilize microtubules, antagonized both of these effects of the microtubule-disrupting agents in the cytolytic lymphocytes. Taxol also antagonized the enhancement of cAMP increases by colchicine in lymphocytes stimulated by 2-chloroadenosine, isoproterenol, and cholera toxin. The enhancement of the prostaglandin El-induced cAMP response caused by treatment of the lymphocytes with either cytochalasin B or 3-deazaadenosine in the presence or absence of L-homocysteine was not antagonized by taxol. Taxol, colchicine, or the combination of these two agents did not affect ATP levels in cytolytic lymphocytes. These results support a modulatory role for microtubules in both the cytolytic process and the production of cAMP in these lymphocytes.Taxol is a natural product diterpenoid that was originally isolated from the plant Taxus brevifolia and was demonstrated to have antitumor and antimitotic activity by Wani et al. (1). Studies in vitro have shown that taxol promotes and stabilizes microtubule assembly (2, 3). Further investigations established that taxol is inhibitory to a number of cellular activities, including fibroblast replication and migration (3), lymphocyte proliferation (4), secretion of plasma proteins by rat hepatocytes (5), human neutrophil spontaneous nondirectional migration as well as response to chemotactic factor (6), and glucose-stimulated insulin secretion by rat islets of Langerhans cells (7). The chemoattractant-induced tyrosinolation of tubulin in rabbit leukocytes (8) and the vincristineinduced shape change, microtubule assembly, and tubulin paracrystal formation in human platelets (9) were also inhibited. Taxol had no effect on Fc-mediated phagocytosis by murine cultured macrophages (10) and did not inhibit mouse lymphocyte capping by anti-Ig (11).Colchicine, a microtubule-disrupting agent, has been reported to inhibit lymphocyte-mediated cytolysis (LMC) (12) and to enhance the hormonal stimulation of cAMP in leukocytes (13). The availability of taxol, a highly active and apparently specific agent, has allowed us to study in more detail the role of microtubules in the cytolytic activity and cAMP metabolism of specifically immune mouse lymphocytes. The results provide additional evidence for the involvement of microtubules in both of these processes and demonstrate that the microtubule-promoting and stabilizing effects of taxol can antagonize these two cellular effects of colchicine and other microtubule-disrupting agents. were added to give a total assay volume of 1.0 ml. The contents of the tubes were mixed, centrifuged at 185 x g for 10 min at room temperature, and incubated for 60 min at 370C. MATERIA...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function.

Wolberg¹,

Stopford²,

Zimmerman³

1984

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Current for the pulse to +50 mV in h is not shown. effective concentration range of this drug suggests that its site ofaction involves microtubules and fast axoplasmic transport (27,28) rather than the channels themselves (29). Thus, intracellular microtubule-based transport of Na channels is probably a prerequisite to insertion in the soma membrane (30,31).…”

mentioning

confidence: 99%

Synthesis of sodium channels in the cell bodies of squid giant axons.

Brismar¹,

Gilly²

1987

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Giant axons in squid are formed by fusion of axons from many small cell bodies in the giant fiber lobe (GFL) of the stellate ganglion. Somata of GFL cells in vivo are inexcitable and do not have measurable sodium current (INa) when studied with microelectrode or patch-electrode voltageclamp techniques. If GFL cells are separated from the giant axons and maintained in primary culture, axon-like INa can be recorded from the somata after several days. Incorporation of Na channels into GFL cell bodies requires protein synthesis, intracellular microtubule-based transport, and the lack of a morphologically defined axon to serve as a sink for channels synthesized in culture.Voltage-controlled Na channels are integral membrane glycoproteins that mediate the electrogenic flow of extracellular Na ions into animal cells and subserve the propagation of action potentials used by neurons for rapid signalling via axons (1). Functional aspects of these proteins (2, 3) and primary structure (4, 5) are known in detail; biochemical (1, 6) and higher-order structural (7) characterization are rapidly progressing. Considerably less is known about the biosynthesis, distribution, and degradation of Na channels, and studies of these phenomena have utilized biochemical (8, 9) and morphological (10) approaches.Voltage-clamp methods provide another excellent probe for detecting functional Na channels because of the high degree of resolution provided (11, 12). Such measurements have been used to map Na channel distribution in skeletal muscle fibers (13,14) and to assess the mobility of channels in the plasma membrane (15). We have undertaken an electrophysiological approach to begin studying the dynamic features of Na-channel cell biology in the numerous cell bodies in the giant fiber lobe (GFL) of the squid's stellate ganglion, which give rise to the giant axon through fusion of their axonal initial segments (16). This system is morphologically simple, experimentally accessible, and the axon has been the subject of extensive investigation (17).Although the many small GFL somata must normally synthesize Na-channel proteins for the giant axons (18), they are inexcitable themselves (19). We find that if these cell bodies are dissociated from the giant axons and maintained in primary culture, Na current (INa) appears within several days. This condition persists for at least 2 weeks and is inhibited by actinomycin D or by demecolcine, a colchicine derivative. Our results suggest that an important step leading to the appearance of operational Na channels in the soma membrane involves intracellular translocation of newly synthesized channels along microtubule pathways. MATERIALS AND METHODSCell bodies (diameter, 20-40 ,um) were isolated from the posterior tip of the giant fiber lobe of stellate ganglia (16,20) in Loligo opalescens and Lolliguncula brevis (21) and maintained in primary culture at 15'C essentially as described by Bookman and coworkers (22,23). Excised GFL tips were treated with nonspecific protease (10 mg/ml, type XIV; Sig...

show abstract

“…Recent studies revealed a wide variety of effects of colchicine on ion-channel activities. Colchicine blocks a type of the K channel in crayfish axons (Terakawa & Watanabe, 1976), the Ca channel in cultured guinea pig neurons (Fukuda et at., 1981), the Na channel in squid giant axons (Matsumoto & Sakai, 1979a;Matsumoto et al, 1980Matsumoto et al, , 1984aChang, 1983;Landowne et al, 1983), or it blocks the Ca, Na and C1 channels in Aplysia neurons (Baux et al, 1981). The diversity of these findings suggest that cytoskeletal proteins influence the activity of ion channels in an indirect way via some unknown factors.…”

Section: Introductionmentioning

confidence: 94%

Are axoplasmic microtubules necessary for membrane excitation?

Terakawa

Nakayama

1985

J. Membrain Biol.

View full text Add to dashboard Cite

The excitability of the squid giant axon was studied as a function of transmembrane hydrostatic pressure differences, the latter being altered by the technique of intracellular perfusion. When a KF solution was used as the internal medium, a pressure difference of about 15 cm water had very little effect on either the membrane potential or excitability. However, within a few minutes after introducing either a KCl-containing, a KBr-containing, or a colchicine-containing solution as the internal medium, with the same pressure difference across the membrane, the axon excitability was suppressed. In these cases, removal of the pressure difference restored the excitability, indicating that the structure of membrane was not irreversibly damaged. Electron-microscopic observations of these axons revealed that the perfusion with a KF solution or colchicine-containing solution preserves the submembranous cytoskeletal layer, whereas perfusion with a KCl or KBr solution dissolves it. These results suggest that the submembranous cytoskeletons including microtubules provide an important mechanical support to the excitable membrane but are not essential elements in channel activities.

show abstract

Colchicine Alters the Nerve Birefringence Response

Abstract: The internal perfusion of squid axons with colchicine reversibly and selectively reduces the transient sodium current and the birefringence response to a brief depolarizing voltage pulse.

Cited by 14 publications

References 11 publications

Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function.

Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function.

Synthesis of sodium channels in the cell bodies of squid giant axons.

Are axoplasmic microtubules necessary for membrane excitation?

Contact Info

Product

Resources

About