HORMONE-MEDIATED CALCIUM RESPONSES IN RAT AND HUMAN HEPATOCYTES - A STUDY OF MULTICELLULAR SYSTEMS BY VIDEOMICROSCOPY

Objectives and methods. - Activation of hepatocyte hormonal receptors leads to the mobilization of intracellular Ca2+ which is thought to be an elaborate system for encoding hormonal messages. We studied hormon e-induced calcium signals in freshly isolated multicellular systems of normal rat and human hepatocytes. Calcium signals were recorded by vi deomicroscopy after stimulation with noradrenaline, angiotensin II, an d vasopressin. Results. - Calcium signals were highly organized in mul tiplets: the different hepatocytes responded to Ca2+-mobilizing hormon es in a sequentially ordered manner, with a first, a second (doublets) and a third (triplets) responding cells. This pattern was an intrinsi c feature of the multicellular systems, and seemed to be a result of a gradual heterogeneity of the sensitivity of the different cells, to t he hormones. The stimulation of the same multiplet with two different agonists and the removal of the hormone during cell responses provides some evidence for the major role of hormonal receptors in this hetero geneity. Conclusions. - Hormone responses in multicellular systems of rat and human hepatocytes are highly elaborate. The density of hormona l receptors could be the major determinant of the sequential pattern o f Ca2+ responses. Hormonal receptors may be gradually distributed amon g the different cells of the multiplets in vitro and along the porto-c entrilobular axis in situ.