Activation of the Vasopressin-sensitive Water Permeability Pathway in the Toad Bladder by N-ethyl Maleimide
|Title:||Activation of the Vasopressin-sensitive Water Permeability Pathway in the Toad Bladder by N-ethyl Maleimide|
|Authors:||Marples, David; Bourguet, J.; Taylor, Ann|
|Date Published:||September 01, 1994|
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 interacts with its receptor, in the granular cell, it stimulates the production of cAMP. This in turn stimulates other molecular processes which cause tiny sacs (aggrephores) carrying specific water channels in their walls to shuttle from inside the cell to the apical membrane of the cell. The aggrephores shuttle along microtubles and microfilaments that in part comprise the skeleton of the cell. The water channels are proteins that, when inserted in the apical membrane, allow water to pass through the membrane.
Marples, et al., after performing a series of experiments on toad bladders, report that the chemical, N-ethyl maleimide (NEM) also increases the flow of body water across the apical membrane. It does not allow as much water as the VP-induced water flow, but both flows have a roughly similar pattern in terms of the time it takes for the water flow to increase.
The researchers found that NEM induced the increase in body water flow across the apical membranes in a manner similar to VP. The NEM-induced water flow is sensitive to the same things that inhibit the VP-induced water flow: acidification of the cell's serosal membrane, and exposure to the drugs quinidine, nocodazole or EHNA. NEM-induced water flow, like that of VP, involves the movement of water channel-bearing aggrephores to the apical membrane.
There were differences. Unlike the VP-induced water flow, the NEM-induced water flow is irreversible. That is, NEM irreversibly activates components of the cellular apparatus required for water flow across the apical membrane. (Thus, even if NEM is removed from the bladder culture, the water flow it initiates continues.) Also, NEM does not stimulate cAMP, nor does it require cAMP to be stimulated to induce the water flow. However, it does require an intact cytoskeleton (i.e. the microfilaments and microtubules that help the aggrephore travel from inside the cell to the cell's apical membrane must be intact and functioning).
The researchers conclude that NEM increases the water permeability of the toad bladder by activating some of the same processes that VP uses. Further experiments with NEM may prove valuable in clarifying the biochemical steps that underlie the action of VP.