CONNEXINS AND GLUCAGON RECEPTORS DURING DEVELOPMENT OF RAT HEPATIC ACINUS

Levels (by immunoblotting) and cell distribution (by immunofluorescence) of connexins (Cxs) and glucagon receptors (GRs) were studied during the ontogeny of the rat liver. Cx32, the main rat liver gap junction protein, was present in fetal hepatocytes, and its abundance increased between the 19th and 21st gestational days. The major increase in Cx32 levels occurred between the 7th and 21st postnatal days, after which adult levels were reached. The adult pattern of distribution of Cx26 and Cx32 was established by the 21st postnatal day. Cx43 was present in the liver capsule and perisinusoidal cells, and its levels did not show significant variations throughout development. Levels of GRs were much lower in fetal than in adult livers. After birth, GRs increased progressively, reaching adult levels at about the 28th postnatal day. In adults, GR immunoreactivity on the plasma membrane of hepatocytes was localized to the region facing the sinusoid and showed a density gradient of distribution along the hemiacinus: high in pericentral regions and decreasing toward more glucogenically active cells located in periportal regions. Because cells of the hepatic acinus communicate via gap junctions, which are permeable to second messengers, we propose that signals transduced by GRs in cells expressing high levels of receptor might spread to cells expressing low levels of receptor, thus maximizing metabolic activation.