Increased gap junctional area in the rat liver after administration of dibutyryl cAMP

Since cAMP has recently been reported to be a possible physiological modulator of cell-to-cell communication, we performed a quantitative freeze-fracture investigation on the hepatocyte gap junctions after administration of a membrane-permeant derivative of this cyclic nucleotide. For this purpose, male rats received two intraperitoneal injections of 100 mg dibutyryl cAMP/kg body weight with a time interval of 2.5 h. Litter mates were injected with saline only. Five hours after the start of the treatment, tissue blocks of the left lateral liver lobe were fixed by immersion and processed for freeze-fracture. By point counting on negatives projected on a square double-lattice test system the relative gap junctional area on contiguous hepatocyte membranes was determined. As compared to control animals, the proportion of the membrane area occupied by gap junctions in dibutyryl cAMP-treated liver parenchyma significantly increased from 4.9% to 6.1%. Within the gap junctions no changes in shape, particle density or packing pattern were observed. Possibly, the enlarged gap junctional area provides structural pathways for the integration of the response of hepatocytes to messages mediated by cAMP.