Cytosolic bile acid binding protein in rat liver: radioimmunoassay, molecular forms, developmental characteristics and organ distribution.

Rat liver efficiently extracts bile acids from the portal blood and rapidly excretes them into bile. Little is known about the process by which bile acids traverse the liver cell from the sinusoidal to the canalicular membrane. In order to begin to define this process, we recently identified a pair of similar monomeric (33 kilodalton) cytosolic bile acid binding proteins (bile acid binders I and II, J. Biol. Chem. 1983; 258:3602-3607, Abstract). These bile acid binders have comparable binding affinities for bile acid as the YaYa and YaYc members of the family of glutathione S-transferases, the previously recognized cytoplasmic bile acid binding protein. We now report the establishment of a sensitive and specific radioimmunoassay which equally detects both bile acid binders I and II. Specificity of the antiserum was verified by the co-purification of bile acid binder immunoreactivity with the bile acid binders. Liver contained the greatest concentration of bile acid binder, where it constituted 0.33% of the total cytosolic proteins. Phenobarbital administration and lithocholate feeding had no significant effect on hepatic bile acid binder content. Examination of the ontogeny of bile acid binder revealed a rapid increase after birth to near adult levels by Day 14. In summary, we have established a sensitive radioimmunoassay for the bile acid binders. Its localization mainly in liver and its increase after birth parallel bile acid transport in the liver.

Hypergastrinemia develops within 24 hours of truncal vagotomy in dogs.

Postvagotomy hypergastrinemia may result from withdrawal of tonic vagal inhibitory mechanism(s) or from G-cell hyperplasia secondary to diminished acid secretion. Early development of hypergastrinemia, after vagotomy, would favor the first mechanism, whereas delayed development would favor the second. We sought to distinguish between these two mechanisms and to determine whether alterations in somatostatin release might mediate postvagotomy hypergastrinemia. We measured plasma concentrations of gastrin and somatostatinlike immunoreactivity basally and in response to meal (pH controlled at 5.5) and to insulin hypoglycemia before and after truncal vagotomy in 11 dogs. Basal and postprandial hypergastrinemia were established within 24 and 48 h after vagotomy, respectively. Basal and meal-stimulated plasma somatostatinlike immunoreactivity concentrations were unaltered by vagotomy, although insulin hypoglycemia-induced rises in plasma somatostatinlike immunoreactivity were abolished by vagotomy. Our data suggest that neither G-cell hyperplasia nor alterations in somatostatin release explain postvagotomy hypergastrinemia in the dog. The observations support the hypothesis that postvagotomy hypergastrinemia results from the withdrawal of a tonic vagal inhibitory mechanism of gastrin release that is independent of somatostatin. Whether the tonic vagal inhibition of gastrin is direct or indirect is unknown.

Gastric response to severe head injury.

We studied the gastric response to severe head injury and multiple trauma in 53 patients admitted to the surgical intensive care unit at the University of Louisville. Twenty-two of the 32 patients with severe head injury could have endoscopy. Each patient had gastritis or duodenitis. Patients with severe head injury had a slightly higher rate of gastric acid secretion than did the other trauma patients without severe head injury, but the difference was not significant. Serum gastrin levels were normal in both groups and did not correlate with intracranial pressure. Pancreatic polypeptide levels were significantly higher in patients with severe head injury compared with the control trauma patients without head injury. Elevations in pancreatic polypeptide may be linked to increases in intracranial pressure. We conclude that erosive gastritis occurs commonly in patients with severe head injury and that severe head injury is associated with a marked increase in pancreatic polypeptide levels in the fasted, nongut-stimulated state. Gastrin levels are within normal limits. Head injury appears to specifically increase pancreatic polypeptide release, probably by influencing autonomic centers in the mid brain. Because the cephalic phase of pancreatic polypeptide release is vagalcholinergic, the data are consistent with the hypothesis that severe head injury increases vagal activity. Participation of vagal adrenergic fibers in this process cannot be excluded.

Somatostatin-14 and -28: clearance and potency on gastric function in dogs.

To examine the significance of somatostatin-14 (S-14) and somatostatin-28 (S-28) in gastric physiology, we compared their relative potencies on acid secretion in the dog. On a molar infusion basis, S-14 and S-28 appeared to be equipotent, causing 50% inhibition of peptone meal-stimulated acid secretion at a dose of 400 pmol . kg-1 . h-1. However, comparison of the plasma half lives (t 1/2) of the two peptides revealed that S-28 disappeared at a much slower rate (t 1/2 = 2.84 +/- 0.15 min, mean +/- SE, n = 7) than S-14 (t 1/2 = 0.57 +/- 0.06 min). When acid-inhibitory effect was compared against increment in plasma concentrations produced by peptide infusion, S-14 was roughly 10-fold more potent than S-28. No alteration of gastrin response to peptone was observed at a dose of S-14 or S-28 that completely abolished acid secretion, suggesting that regulation of acid secretion is not mediated by gastrin inhibition. Thus, S-14 is a potent and possibly important physiological inhibitor of gastric acid secretion. Although circulating S-28 may have importance in regulation of some biological functions, it appears to play a less prominent role in regulation of gastric secretion.