Comparison of the effects of increased intracellular calcium and antidiuretic hormone on active sodium transport in frog skin. A study with the calcium ionophore A23187

Abstract The dense tubular system (DTS) functions to regulate platelet activation by sequestering or releasing calcium, similar to the sarcotubules of skeletal muscle. In resting platelets, the DTS exists as thin elongated membranes. Within 10 seconds of the addition of thrombin, platelets show a major ultrastructural change in their DTS: from the thin elongated form to a rounded vesicular form. These morphologic changes were demonstrated with two different stains and two different fixation methods. Platelets exposed to the calcium ionophore A23187 showed the same ultrastructural changes in the DTS. In contrast, the DTS remains in a thin elongated form when platelets are stimulated by the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and oleoylacetylglycerol (OAG). These morphologic changes may be related to the discharge of calcium from the DTS because this is stimulated by thrombin and A23187, but not by PMA. Preincubation of the platelets with the intracellular calcium chelator 5,5′-dimethyl-bis-(0- aminophenoxy)-ethane-N,N,N′,N tetra acetic acid (BAPTA) largely prevented both the thrombin-induced rise in intracellular calcium and the changes in DTS morphology, suggesting that the changes in DTS morphology are secondary to the increase in cytosolic calcium. The results provide a morphologic correlate to existing biochemical evidence showing that the DTS is involved early during paltelet activation.

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Is a rise in intracellular concentration of free calcium necessary or sufficient for stimulated cytoskeletal-associated actin?

The Journal of Cell Biology ◽

10.1083/jcb.102.4.1459 ◽

1986 ◽

Vol 102 (4) ◽

pp. 1459-1463 ◽

Cited By ~ 73

Author(s):

R I Sha'afi ◽

J Shefcyk ◽

R Yassin ◽

T F Molski ◽

M Volpi ◽

...

Keyword(s):

Intracellular Calcium ◽

Pertussis Toxin ◽

Incubation Medium ◽

Calcium Ionophore ◽

Calcium Ionophore A23187 ◽

Extracellular Calcium ◽

Intracellular Concentration ◽

The Other ◽

Free Calcium ◽

Ionophore A23187

The addition of the calcium ionophore A23187 to rabbit neutrophils increases the amount of actin associated with the cytoskeleton regardless of the presence or absence of calcium in the incubation medium. In the presence of extracellular calcium, the effect of A23187 is biphasic with respect to concentration. The action of the ionophore is rapid, transient, and is inhibited by pertussis toxin, hyperosmolarity, and quinacrine. On the other hand, the addition of pertussis toxin or hyperosmolarity has small if any, effect on the rise in intracellular calcium produced by A23187. While quinacrine does not affect the fMet-Leu-Phe-induced increase in cytoskeletal actin and the polyphosphoinositide turnover, its addition inhibits completely the stimulated increase in Ca-influx produced by the same stimulus. The results presented here suggest that a rise in the intracellular concentration of free calcium is neither necessary nor sufficient for the stimulated increase in cytoskeletal-associated actin. A possible relationship between the lipid remodeling stimulated by chemoattractants and the increased cytoskeletal actin is discussed.

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The effect of small hydrostatic pressure gradients on the rate of active sodium transport across isolated living frog-skin membranes

The Journal of Physiology ◽

10.1113/jphysiol.1968.sp008442 ◽

1968 ◽

Vol 195 (1) ◽

pp. 1-18 ◽

Cited By ~ 23

Author(s):

D. M. Nutbourne

Keyword(s):

Hydrostatic Pressure ◽

Sodium Transport ◽

Frog Skin ◽

Pressure Gradients ◽

Active Sodium ◽

Active Sodium Transport

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The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs

Journal of Neurosurgery ◽

10.3171/jns.1986.65.1.0080 ◽

1986 ◽

Vol 65 (1) ◽

pp. 80-85 ◽

Cited By ~ 84

Author(s):

Masakazu Takayasu ◽

Yoshio Suzuki ◽

Masato Shibuya ◽

Toshio Asano ◽

Masahiko Kanamori ◽

...

Keyword(s):

Blood Pressure ◽

Intracellular Calcium ◽

Cerebral Vasospasm ◽

Basilar Artery ◽

Calcium Antagonists ◽

Calcium Ionophore ◽

Calcium Ionophore A23187 ◽

Ionophore A23187 ◽

Delayed Cerebral Vasospasm ◽

Arterial Blood

✓ The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquino-linesulfonamide) and HA1077(l-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 × 10−6 M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10−5 M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10−5 M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a “two-hemorrhage” canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% ± 2% (mean ± standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

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