Extracellular Ca2+ and the effect of antidiuretic hormone on the water permeability of the toad urinary bladder: an example of flow-induced alteration of flow.

The extracellular Ca2+ requirement for antidiuretic hormone (ADH) stimulation of water permeability in the toad urinary bladder has been critically examine. The polarity of the tissue was maintained with 1 mM Ca2+ in the mucosal bathing medium and a serosal bath nominally free of Ca2+. Under these conditions, ADH-induced osmotic water flow was inhibited by more than 60% while enhancement of the diffusional permeability to water was unaffected. Structural studies revealed that low serosal Ca2+ led to parallel alterations in epithelial architecture that amounted to a significant distortion of the osmotic water pathway. Prevention of these alterations, or restoration of normal cell-cell contact showed that the reduction of serosal Ca2+ did not restrict hormonal action per se, but that it resulted in a weakening of cell-cell junctions such that intercellular space distension during water flow occurred to a point where the geometric conditions for maintenance of osmotic flow were compromised. We conclude that extracellular Ca2+ is not a requirement for the molecular aspects of ADH action but that, in its absence, a direct measurement of ADH-induced osmotic flow proves to be an inaccurate index of the hormone-generated changes in epithelial transport characteristics. Under certain conditions the ADH-effect on the tissue's hydraulic permeability is probably best assessed by measurement of the diffusional permeability to water; although accuracy in this determination is difficult, it is not as strongly dependent on tissue geometry.