Effect of alpha-adrenergic blockers on calmodulin association with the nuclear matrix of rat liver cells during proliferative activation.

A transient peak of cytosolic calmodulin (CaM) was produced during the prereplicative phase of rat liver cell proliferation following partial hepatectomy. After accumulating in the cytosol, CaM apparently translocated into the nuclei, associating with the nuclear matrix. The administration of alpha 1-adrenergic blockers to hepatectomized rats prevented the association of CaM with the nuclear matrix without affecting the increase in the total nuclear CaM. The inhibitory effect of the alpha 1-antagonists was reversed by the simultaneous injection of the alpha-agonist noradrenaline. Since the activation of alpha 1-adrenergic receptors results in the release of Ca2+ from endoplasmic reticulum stores, the results suggest that the association of CaM with the nuclear matrix during proliferative activation is mediated by Ca2+ released from endoplasmic reticulum and show that the association with the matrix is independent of its intranuclear accumulation.