Hormone receptor gradients supporting directional Ca2+ signals: direct evidence in rat hepatocytes

In the liver, InsP(3)-dependent agonists such as vasopressin and noradrenaline induce tightly coordinated sequences of intracellular Ca(2+) increases, leading to apparent unidirectional Ca(2+) waves. In previous works, we have postulated that cell-to-cell differences in hormone receptor density create a cellular sensitivity gradient that determines which cell initiates the intercellular Ca(2+) wave and the direction of propagation of the Ca(2+) signal. The aim of this study was to test directly this hypothesis.

Lobular distribution of V1a vasopressin receptors and alpha1 adrenergic receptors were observed by autoradiography in rat liver sections. Cell-to-cell differences in the number of these receptors were evaluated on hepatocyte multiplets using specific fluorescent probes.

The relative amount of fluorescence associated with the V1a receptor differed significantly between cells within multiplets. The 'cell-after-cell' Ca(2+) increase induced by vasopressin was correlated with the number of V1a receptors. These observations may be more general, as autoradiography revealed similar lobular distributions of V1a receptors and alpha1 adrenergic receptors; the amounts of both were greatest in hepatocytes surrounding central veins.

These data confirm that a fine gradient along liver cell plates contributes to the molecular basis of the unidirectional hormone-induced Ca(2+) signalling observed in the liver lobule.