Hepatic inactivation of vasoactive intestinal peptide in man and dog.
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.
D000818:Animals; D000941:Antigens; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D009388:Neostigmine / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D011167:Portacaval Shunt, Surgical; D011169:Portal Vein / Q000378:metabolism; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014680:Veins
D000941:Antigens; D005768:Gastrointestinal Hormones; D014660:Vasoactive Intestinal Peptide; D009388:Neostigmine; D010418:Pentagastrin; D002118:Calcium