Regulation of Membrane Permeability by Vasopressin; Activation of the Water Permeability Pathway in Toad Urinary Bladder by N-Ethyl-Maleimide
| Title: | Regulation of Membrane Permeability by Vasopressin; Activation of the Water Permeability Pathway in Toad Urinary Bladder by N-Ethyl-Maleimide |
|---|---|
| Authors: | Taylor, Ann; Marples, David |
| Publisher: | Comparative Biochemistry & Physiology. A Comparative Physiology |
| Date Published: | January 01, 1988 |
| Reference Number: | 397 |
1. Vasopressin induces a rapid increase in water permeability and stimulates net sodium transport in responsive epithelia through the mediation of cAMP. 2. In amphibian urinary bladder, the increase in water permeability is dependent on an intact cytoskeleton and is associated with the exocytotic insertion of tubular vesicles containing particle aggregates (the putative water channels) into the apical membrane of the granular epithelial cells. 3. In the toad bladder, mucosal addition of NEM, 0.1 mM, elicits a slow and irreversible increase in transepithelial water flow, whilst decreasing net sodium transport. 4. The hydrosmotic response to mucosal NEM is inhibited by cellular acidification, by pretreatment with cytoskeleton-disruptive drugs, and by agents that increase cytosolic calcium. 5. Mucosal NEM potentiates the hydrosmotic response to a submaximal, but not a maximal, dose of vasopressin. 6. Mucosal NEM, like vasopressin, induces both vesicle fusion and the appearance of particle aggregates at the granular cell apical surface. 7. NEM, unlike vasopressin, does not increase cellular cAMP content. 8. Mucosal NEM appears to increase transcellular water flow by activating cellular processes normally triggered by vasopressin, at a step beyond cAMP.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
When VP binds with its receptors, it stimulates the enzyme, adenylyl cyclase (AdC). This raises levels of the metabolic regulator, cyclic adenosine monophosphate (cAMP). Some researchers think that cAMP then activates protein kinase A (PKA), which phosphorylates (introduces a phosphate group to) specific cellular proteins. This leads to specific proteins called water channels (WCs), encased in tiny sacs called vesicles, to move to and fuse with the apical membrane. Once the WC-containing vesicles are fused with the membrane, the WCs are inserted into it. The WCs act as channels through which water can pass across the membranes. When VP absents itself from the cell, the WCs are removed from the membrane, returned in vesicles back to the inside of the cell, and the apical membrane reverts back to its low (Pf).
There is now evidence that the granular cell's cytoskeleton (the cytoplasm's internal structural reinforcement) plays an important role in the structural events underlying the VP-induced Pf increase. Researchers now think that microtubules help the WC-bearing vesicles move toward the apical membrane at the onset of VP stimulation. Microfilaments may be involved in the restructure of the cytoplasm near the apical membrane and in the redistribution of the WCs over the apical membrane after they have been inserted into it.
Like VP, the substance N-ethyl-maleimide (NEM) can, when properly applied to the toad granular cell, increase the water flow across bladder tissue. There are some differences, however.
- The NEM-induced increases in water flow is smaller and develops more slowly than the VP-induced flow.
- The NEM-induced water flow is not rapidly reversed when NEM is removed, whereas the VP-induced water flow is rapidly revised upon VP removal.
- Whereas the VP-induced flow involves elevated levels of cAMP, NEM's does not. NEM actually decreases cAMP levels, so it is unlikely that NEM activates AdC in order to increase Pf.
There are, however, similarities between NEM- and VP-induced increases in water flow.
- They both require a similar pH in the cell.
- Both are inhibited by high cellular calcium levels, which interfere with the cytoskeletal structural events that help the WCs travel to, fuse with and spread through the apical membrane.
- NEM, like VP, induces both vesicle fusion and appearance of WC vesicles at the apical membrane.
The compiled research results suggest that, in increasing the water flow across the apical membrane, NEM uses the same, but not all of the cellular structures and molecular sequence triggered by VP. The molecular sequence NEM uses dovetails with the sequence initiated by VP at a step beyond the activation of cAMP, for NEM does not activate cAMP. The authors conclude that NEM may be helpful in clarifying some of the steps of the molecular sequence initiated by VP to increase apical membrane Pf.