To what extent is microtubular network involved in antidiuretic response?
Antimitotic drugs markedly interfere with antidiuretic response, strongly implying that cytoskeleton integrity is essential to this function. This role of the cytoskeleton in controlling the epithelial transport has been seen as a necessary step in the translocation of the water channel containing particle aggregates and in their delivery to the apical membrane. We have now reexamined the exact role of the microtubular network by appropriate time course determinations, by the use of microtubule disruptive agents that lack of the side effects of colchicine, and by trying to visualize the apparent modifications of the microtubular network that accompany water permeability alterations using immunocytochemical techniques. Our results fully confirm that after microtubular network disruption, antidiuretic hormone-induced water permeability variations undergo typical alterations consisting in both a reduction in peak net water flow and a slowing down of its onset. At the same time, the microtubular network disappears in all the epithelial cells. We also show that colchicine-induced inhibition can still be observed in the presence of a prostaglandin synthetase inhibitor and that this inhibition is most likely to occur at a post-adenosine 3',5'-cyclic monophosphate level. These data, as well as results from other series with nocodazole, indicate that the reduction of the net water flow directly results from microtubular network disruption and not from side effects of the disrupting drugs. They also show that the hydrosmotic response is only partially dependent on the microtubular network, which probably has only a guidance role in the translocation of particle aggregates and their exocytotic fusion to the apical membrane.
Valenti
G
G
Département de Biologie, Centre d'Etudes Nucléaires de Saclay, Gif sur Yvette, France.
Hugon
J S
JS
Bourguet
J
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015739:Nocodazole; D010121:Oxytocin / Q000494:pharmacology; D011893:Rana esculenta; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D001562:Benzimidazoles; D015124:8-Bromo Cyclic Adenosine Monophosphate; D010121:Oxytocin; D015739:Nocodazole; D003078:Colchicine; D007213:Indomethacin