Bile acid-independent bile flow is differently regulated by glucagon and secretin in humans after orthotopic liver transplantation

Abstract

The present study characterizes recovery of bile secretion after orthotopic liver transplantation (OLT) in humans with special regard to hormonal regulation of bile acid-independent bile flow by glucagon and secretin. Sixty-seven patients with an uncomplicated postoperative course were studied during the first 3 weeks after OLT to determine normalization of bile flow. A group of 7 and 10 patients, respectively, underwent a biliary stimulation test by either glucagon at days 7, 14, and 21 after OLT or by secretin at days 2, 10, and 21 after OLT. Secretin tests were similarly performed in patients with acute severe rejection during the first 10 days after OLT, while glucagon tests were performed in patients with acute allograft rejection occurring 2 weeks after OLT. Furthermore, hormone effects were studied in nontransplanted patients after cholecystectomy with indwelling biliary T tube. After OLT, bile secretory function recovered and stabilized within 14 days after surgery by reconstitution of both bile acid-dependent and -independent bile flow. Two weeks after OLT, bile secretion was comparable with nontransplanted patients after cholecystectomy. Glucagon and secretin stimulated bile acid-independent bile flow in transplanted and nontransplanted patients significantly, yet secretin choleresis, unlike glucagon choleresis, had already occurred during the first days after OLT and was unaffected by acute allograft rejection. These results allow the speculation that, in humans, glucagon and secretin exert their choleretic activity by different mechanisms and/or at different anatomical sites in the liver. Assuming that secretin acts at the bile duct cells, its secretory capacity was not altered by the transplantation procedure and during moderate or severe rejection episodes, as opposed to glucagon choleresis, which most likely originates in the hepatocytes and requires an entirely reconstituted canalicular transport system after OLT.

Investigation of the effects of peppermint oil and valerian on rat liver and cultured human liver cells

“…secretin) and neural factors (e.g. via the vagus nerve) 17–20 . However, further experiments would be required to determine the mechanism of action of high‐dose peppermint oil on bile flow rate.…”

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

“…During BDL-mediated cholestasis, bile acid metabolism is significantly altered in hepatocytes and cholangiocytes. (15,21,22) These changes, however, do not necessarily affect the amount of biliary fluid generated in the bile canalicular network, (23,24) but rather only the bile salt concentrations. We investigated whether the increase in the overall length of bile ducts and the number of branches post-BDL also lead to enhanced connectivity of the lobular canalicular network.…”

Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl− transport in biliary epithelial cells through a PKCζ‐dependent pathway

“…osmotic gradients, uptake of organic solutes or bile acids (Lira et al 1992; Lazaridis et al 1997)), pressure/distention due to pathological conditions associated with biliary obstruction, and flow/shear forces at the apical membrane due to changes in bile flow. The hormone secretin, for example, increases bile flow from 0.67 to 1.54 ml min −1 in humans (Lenzen et al 1997), representing a potential increase in flow‐induced force at the apical cholangiocyte membrane. Recently, it has been shown in isolated rat bile duct segments that flow significantly increases [Ca 2+ ] i (Masyuk et al 2006).…”