vasoactive-intestinal-peptide and Hepatic-Encephalopathy

Topics: Adult; Aged; Female; Gastrins; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Male; Middle Aged; Neurotensin; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

Recent studies have suggested that decreased excitatory neurotransmission in the brain may contribute to the overall neural inhibition which characterizes the syndrome of hepatic encephalopathy (HE), and that vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK) may promote neural excitation in the brain. To determine if brain levels of these neuropeptides are altered in HE, measurements were made of the concentrations of immunoreactive VIP (iVIP) and immunoreactive CCK (iCCK) in cerebral cortex, cerebellum and hypothalamus isolated from normal rabbits and rabbits with galactosamin-induced hepatic coma. Hepatic coma was associated with reduced concentrations of iVIP, small molecular weight iCCK and large molecular weight iCCK in the cerebral cortex but not in the cerebellum or hypothalamus. These findings are compatible with decreased VIP- and CCK-mediated neural excitation occurring in the syndrome of HE.

Topics: Animals; Brain; Cerebellum; Cerebral Cortex; Cholecystokinin; Galactosamine; Hepatic Encephalopathy; Hypothalamus; Molecular Weight; Rabbits; Vasoactive Intestinal Peptide

Topics: Animals; Crohn Disease; Gastrointestinal Diseases; Gastrointestinal Hormones; Hepatic Encephalopathy; Humans; Hypertension; Rats; Receptors, Cell Surface; Vasoactive Intestinal Peptide

Topics: Amino Acids, Branched-Chain; Animals; Dogs; Gastrointestinal Hormones; Haplorhini; Hepatic Encephalopathy; Liver Diseases; Portacaval Shunt, Surgical; Vasoactive Intestinal Peptide

IN AN EFFORT TO DOCUMENT THE ROLE OF THE LIVER IN THE CATABOLISM OF VASOACTIVE INTESTINAL PEPTIDE, SEVERAL DIFFERENT TYPES OF EXPERIMENTS WERE CARRIED OUT, INCLUDING: 1) simultaneous measurement of portal and systemic immunoreactive vasoactive intestinal peptide, both in the basal state and following calcium stimulation; 2) by measuring plasma concentrations of immunoreactive vasoactive intestinal peptide before and after portacaval shunt; 3) by measuring plasma VIP before and after portacaval shunt following calcium, prostigmine and pentagastrin stimulation; 4) by determining plasma VIP levels in patients with liver disease and in hepatic failure, and in patients with variceal hemorrhage before and serially after portal systemic shunt; 5) by measuring CSF vasoactive intestinal peptide in dogs before and after portacaval shunt and when the animals finally succumb to hepatic failure. The results consistently suggest that the shunting of portal blood away from the liver does not result in significant elevation of basal peripheral plasma levels of vasoactive intestinal peptide. Following stimulation however, increased amounts of peripheral plasma VIP are detected, following calcium, pentagastrin and prostigmine release of VIP. Portal vein levels are always significantly higher than peripheral plasma VIP again, confirming a catabolic role for the liver. In patients, elevation of peripheral plasma VIP is seen in hepatic failure, but not after portacaval shunt. Finally, cerebrospinal fluid VIP is elevated in dogs following hepatic failure, confirming the presence of a neural-gut axis and suggesting an influence of hepatic catabolism of VIP not only in the periphery, but also within the central nervous system.

Topics: Animals; Antigens; Calcium; Dogs; Gastrointestinal Hormones; Hepatic Encephalopathy; Humans; Liver; Liver Diseases; Neostigmine; Pentagastrin; Portacaval Shunt, Surgical; Portal Vein; Stimulation, Chemical; Vasoactive Intestinal Peptide; Veins