Effect of cytochalasin B on intestinal smooth muscle cells

Obara, Kazuo; Yabu, Hideyo

doi:10.1016/0014-2999(94)90092-2

Cited by 43 publications

(42 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a similar study, when actin polymerization was blocked by CB, K ϩ -induced contraction of intestinal smooth muscle cells was inhibited in a dosedependent manner, without any significant effect on voltagedependent calcium channels, membrane potential, or myosin light chain phosphorylation, indicating an influence of actin assembly on smooth muscle contraction. 33 The present study, however, suggests for the first time that myogenic responses (ie, pressure-dependent contraction) of cerebral arteries was diminished when actin polymerization was blocked by CB.…”

Section: Discussionmentioning

confidence: 69%

Vascular Smooth Muscle Actin Cytoskeleton in Cerebral Artery Forced Dilatation

Cipolla

Osol

1998

Stroke

View full text Add to dashboard Cite

Background and Purpose-We investigated the role of actin polymerization in regulating arterial diameter in response to increasing pressure and modulating forced dilatation of cerebral arteries at pressures above the upper limit of autoregulation. Methods-Posterior cerebral arteries (nϭ12) were isolated and pressurized in a special arteriograph that allowed control of intravascular pressure and measurement of lumen diameter. Intact arteries in the absence (control) or presence of 3.0 mol/L cytochalasin B (CB), an inhibitor of actin polymerization, were subjected to stepwise increases in pressure from 75 to 200 mm Hg. Lumen diameter was continuously recorded, as was the pressure at which forced dilatation (loss of tone) occurred. After a period of time at 200 mm Hg, pressure was returned to 75 mm Hg and the extent of tone recovery was evaluated. Results-Arteries with and without CB developed a similar amount of tone during equilibration at 75 mm Hg: percent toneϭ27Ϯ3% for control versus 29Ϯ4% for CB arteries (PϾ0.05). However, arteries in the presence of CB could not withstand pressure as well and underwent FD at significantly lower pressures: 168Ϯ5 mm Hg for control versus 142Ϯ5 mm Hg for CB arteries (PϽ0.01). The amount of tone that arteries regained after FD when pressure was returned to 75 mm Hg was also less in CB arteries: percent toneϭ34Ϯ3% for control versus 11Ϯ2% for CB arteries (PϽ0.01). Conclusions-Cytoskeletal integrity appears important for maintaining cerebral arterial diameter during changing intravascular pressure. In addition, the process of actin polymerization may be a significant contributor to development of myogenic tone after forced dilatation. (Stroke. 1998;29:1223-1228.)

show abstract

Section: Discussionmentioning

confidence: 69%

Vascular Smooth Muscle Actin Cytoskeleton in Cerebral Artery Forced Dilatation

Cipolla

Osol

1998

Stroke

View full text Add to dashboard Cite

show abstract

“…It should be kept in mind that toxin B-induced inhibition of force could be due to mechanisms unrelated to specific intracellular signalling pathways involved in the process of Ca¥ sensitization. The effect of toxin B on the cellular morphology is similar to that of cytochalasins which are known to disrupt the actin cytoskeleton and inhibit tension development in smooth muscle (Adler, Krill, Alberghini & Evans, 1983;Obara & Yabu, 1994). If toxin B-induced inhibition of force was due to a dissociation of actin filaments we would, however, expect that both peak 1 and peak 2 would be inhibited.…”

Section: Discussionmentioning

confidence: 77%

Clostridium difficile toxin B inhibits carbachol‐induced force and myosin light chain phosphorylation in guinea‐pig smooth muscle: role of Rho proteins

Lucius

Arner

Steusloff

et al. 1998

The Journal of Physiology

View full text Add to dashboard Cite

1. Clostridium difficile toxin B glucosylates the Ras-related low molecular mass GTPases of the Rho subfamily thereby inactivating them. In the present report, toxin B was applied as a tool to test whether Rho proteins participate in the carbachol-induced increase in the Ca¥ sensitivity of force and myosin light chain (MLC) phosphorylation in intact intestinal smooth muscle. 2. Small strips of the longitudinal muscle of guinea-pig small intestine were incubated in toxin B (40 ng ml¢) overnight. Carbachol-induced force and intracellular [Ca¥], and, in a separate series, force and MLC phosphorylation, were determined. 3. Carbachol induced a biphasic contraction: an initial rapid increase in force (peak 1) followed by a partial relaxation and a second delayed increase in force (peak 2). The peak of the Ca¥ signal measured with fura_2 preceded peak 1 of force and then declined to a lower suprabasal steady-state level. Peak 2 was not associated with a significant increase in [Ca¥]. Toxin B nearly completely inhibited peak 2 while peak 1 was not significantly inhibited. Toxin B had no effect on the Ca¥ transient. 4. In control strips, MLC phosphorylation at peak 2 was 27·7%, which was significantly higher than the resting value (18·6%). The inhibition of the second, delayed, rise in force induced by toxin B was associated with complete inhibition of the increase in MLC phosphorylation. The resting MLC phosphorylation was not significantly different from that of the control strips. 5. The initial increase in MLC phosphorylation determined 3 s after exposure to carbachol was 54% in the control strips. Toxin B also inhibited this initial phosphorylation peak despite the fact that the Ca¥ transient and the initial increase in force were not inhibited by toxin B. This suggests that Rho proteins play an important role in setting the balance between MLC phosphorylation and dephosphorylation reactions even at high levels of intracellular Ca¥. 6. These findings are consistent with the hypothesis that the delayed rise in force elicited by carbachol is due to an increase in the Ca¥ sensitivity of MLC phosphorylation mediated by Rho proteins.

show abstract

“…The pharmacologic agents latrunculin and cytochalasin, which inhibit actin polymerization by sequestering G-actin monomers and by capping actin filaments, respectively (17,32,35), have been widely employed in a variety of smooth muscle tissue and cell types to evaluate the effects of inhibiting actin polymerization on contractile responses to agonist stimulation. Studies of airway smooth muscle (6,43,84,115,131,140), vascular smooth muscle (1,25,27,28,92,93,104,107,112,138), and uterine (112) and intestinal smooth muscle (81,91) have all shown that the short-term exposure of smooth muscle tissues to inhibitors of actin polymerization causes a profound suppression of tension development and an inhibition of shortening or constriction. Additional evidence that actin polymerization plays a critical role in the process of mechanical tension development in smooth muscle comes from studies showing that molecular constructs or peptides that disrupt specific steps in the actin polymerization process also inhibit tension development in smooth muscle tissues in response to contractile stimuli (7,123,127,128,143,144).…”

Section: Actin Polymerization Is Necessary For Contraction and Tensiomentioning

confidence: 99%

“…Subsequent studies of the effects of inhibiting actin polymerization in a number of other smooth muscle tissues have led to similar conclusions. Studies of rat mesenteric arteries (25,93), guinea pig taenia coli (91), and airway smooth muscle tissues (84) have demonstrated that tension development can be substantially inhibited by cytochalasin and/or latrunculin with no detectable effect on myosin light chain phosphorylation. Furthermore, Shaw et al (112) showed that phenylephrine-induced increases in intracellular Ca 2ϩ in rat mesenteric arteries were not inhibited when constriction was inhibited by cytochalasin or latrunculin.…”

Section: Stimulus-induced Actin Polymerization Does Not Regulate Actimentioning

confidence: 99%