Vasopressin receptor distribution in the liver controls calcium wave propagation and bile flow

Arginine vasopressin elicits elaborate Ca 2 + signals in the liver (intercellular Ca 2 + waves), the functional implications of which are not understood. Waves propagate across hepatocyte plates following a lobular gradient in Via vasopressin receptor density. Here, we report that changes in this receptor distribution control Ca 2 + wave propagation and bile flow. Although basal circulating vasopressin levels do not play a major role in the regulation of V1a receptor expression, increases in vasopressin concentration within physiological limits for 24 h can abolish the lobular gradient in V1a receptor, as assessed by spectrofluorimetry, videomicroscopy, binding studies, and RNase protection assays. In animals in which the V1a receptor gradient was abolished, intercellular Ca 2 + waves were impaired due to the equalization of Ca 2 + responses in the various zones of the lobule. In the isolated perfused liver, the early increase in vasopressin‐induced bile flow observed in control rats was much smaller if the V1a receptor density gradient was abolished. These findings suggest that V1a vasopressin receptor distribution controls intercellular Ca 2 + wave propagation and bile flow. The control of hormone receptor distribution in a tissue by an agonist may turn the signaling and function of this agonist on or off.