Communication via gap junctions modulates bile secretion in the isolated perfused rat liver

Background & Aims: Bile secretion is regulated in part by adenosine 3',5'-c yclic monophosphate (cAMP) and cytosolic Ca2+ (Ca-i(2+)). Hormone receptors that link to these second messengers are not uniformly distributed across the hepatic lobule, but both cAMP and Ca-i(2+) cross gap junctions, so we t ested whether gap junctional communication plays a role in changes in bile flow induced by the activation of these receptors, Methods: cAMP levels in isolated perfused rat livers were increased by usin g glucagon, because glucagon receptors are predominantly on pericentral hep atocytes, or by using dibutyryl cAMP, which acts on hepatocytes throughout the hepatic lobule, Ca-i(2+) concentration was increased by using vasopress in, because V-1a receptors are most heavily expressed on pericentral hepato cytes, or by using 2,5-di(tert-butyl)-1,4-benzo-hydroquinone (t-BuBHQ), whi ch increases the Ca-i(2+) concentration in hepatocytes throughout the hepat ic lobule. We used 18 alpha-glycyrrhetinic acid (alpha GA) to block gap jun ction conductance, which was assessed by fluorescence recovery after photob leaching. Results: alpha GA blocked fluorescence recovery after photobleaching withou t altering the basal rate of bile flow, Glucagon and dibutyryl cAMP increas ed bile flow; alpha GA blocked the glucagon-induced increase but not that i nduced by dibutyryl cAMP, Vasopressin and t-BuBHQ decreased bile flow; alph a GA exacerbated the decrease induced by vasopressin but not by t-BuBHQ, Conclusions: Glucagon and vasopressin modulate bile flow in a manner that d epends in part on gap junctional communication, even though the two hormone s activate second messengers with opposing effects on bile flow. The organi zation of second messenger signals across the hepatic lobule may be an impo rtant component of hormonal regulation of bile secretion.