Active immunization against somatostatin alters regulation of gastrin in response to gastric acid secretagogues
13
Citation
27
Reference
10
Related Paper
Citation Trend
Abstract:
We have examined the coupling between somatostatin, gastrin, and gastric acidity, using sheep chronically immunized against somatostatin. All immunized sheep had high-titer (3.2 × 105 ± 1.1 × 104 M), high-affinity (1.5 × 1011± 1.2 × 1010 l/mol) antibodies. However, basal gastrin and gastric acidity were similar to those in control animals, indicating that an inhibitory somatostatin tone was not required for the maintenance of normal basal gastrin and gastric acidity. Omeprazole (a proton pump inhibitor) increased gastric pH to a similar extent in both the control and immunized groups but resulted in a smaller increase in plasma gastrin in the immunized sheep, thus calling into question the assumption that hypergastrinemia associated with hypochlorhydria is the result of somatostatin withdrawal. Pentagastrin- or histamine-stimulated somatostatin secretion reversed or attenuated the omeprazole-induced hypergastrinemia in control but not immunized sheep, demonstrating a functional role for somatostatin and the biological efficacy of the somatostatin immunization. In a separate series of omeprazole-treated sheep, restoration of an acidic gastric pH with intragastric HCl reversed the hypergastrinemia in both control and immunized animals. We conclude that somatostatin is not essential for the acid-mediated regulation of gastrin. The use of a chronically immunized model as opposed to the acute administration of somatostatin antibodies has important advantages in determining the steady-state regulatory role of somatostatin.Keywords:
Pentagastrin
Basal (medicine)
The effect of oral omeprazole on pentagastrin stimulated gastric acid secretion was studied in 11 healthy subjects. Doses of 20-80 mg produced dose dependent inhibition of acid secretion, with total suppression at the highest dose. Omeprazole was absorbed and eliminated from plasma rapidly and the inhibitory effect was related to the area under the plasma concentration time curve. The duration of action was long and single doses of 20 and 40 mg reduced acid secretion significantly for one and three days, respectively. Omeprazole in a dose of 15 mg given once daily for five days, suppressed acid secretion continuously, the inhibitory effect stabilising after three days at a predose inhibition of about 30% and a postdose inhibition of about 80%.
Pentagastrin
Cite
Citations (505)
Somatostatin inhibited gastric acid secretion significantly in three ZE patients, while serum gastrin was lowered only in two. A direct inhibition of pentagastrin-stimulated acid secretion by somatostatin was demonstrated in three healthy volunteers and four patients with duodenal ulcer disease. Somatostatin reduced betazole-stimulated gastric acid secretion to a lesser degree. The immunohistological demonstration of somatostatin-producing cells apposite to antral G-cells suggest a physiological role of somatostatin in the regulation of gastrin secretion in man.
Pentagastrin
Sham feeding
G cell
Cite
Citations (1)
Pentagastrin
Cite
Citations (1)
Gastric acid secretion, as well as gastrin and pancreatic peptide release into the bloodstream before and after TV or HSV were observed in 28 patients following modified sham feeding (MSF) and pentagastrin tests. Prior to surgery the majority of patients showed stimulation of gastric acid secretion and hormone release into the bloodstream as the result of the employed tests. The MSF-induced acid output (SAO) and pentagastrin-induced acid output (PAOpg) values were mainly observed immediately following the stimulus. In the majority of patients MSF triggered an increase in blood gastrin and PP concentrations. Nevertheless, the peak concentration values for the two hormones occurred at different time intervals following the stimulus. For gastrin the peak values appeared later than SAO, whereas for PP they occurred either in the course of or immediately after MSF. Irrespectively of, the type of surgical procedure used and the completeness of vagotomy, the values of BAO, PAO, SAO and PAOpg were significantly lower following the procedure. Blood hormone concentration, however, showed greater variations. The test stimulated gastrin release showed the peak values were greater after, than prior to, the surgery, whereas PP release was markedly inhibited. No correlation was found between gastric acid secretion, blood serum gastrin and PP levels.
Pentagastrin
Sham feeding
Pancreatic polypeptide
Gastrointestinal hormone
Cite
Citations (3)
We have studied the capacity of several mammalian tissues to inactivate synthetic human gastrin I and its synthetic analog, pentagastrin. Slices of each tissue studied were incubated with either gastrin or pentagastrin and the degree of inactivation was determined by both radioimmunoassay and bioassay. The results demonstrate that there is an in vitro potential for the inactivation of gastrin in all the tissues tested. There was a close correlation between the results obtained with radioimmunoassay and those obtained with bioassay.
Pentagastrin
Cite
Citations (7)
Pentagastrin
G cell
Parietal cell
Cite
Citations (1)
Abstract The log dose-response curves for graded doses of the secretagogues porcine gastrin (a partially purified sample; the crude and its gastrin II equivalent), histamine, and a gastrin pentapeptide (pentagastrin) on the perfused stomachs of urethanized rats are parallel. On weight basis, pentagastrin is 60 times and histamine four times more active than the crude porcine gastrin preparation. The partially purified porcine gastrin sample is six times more potent than histamine but half as potent as pentagastrin. On molar basis gastrin (as the pure porcine gastrin II) has 3000 times the activity of histamine dihydrochloride and 5000 times that of the histamine base. Gastrin is 50 times more potent than pentagastrin. Gastrin and pentagastrin are more potent and have less undesirable side-effects than histamine.
Pentagastrin
G cell
Pentapeptide repeat
Cite
Citations (5)
G cell
Gastrointestinal hormone
Cite
Citations (12)
SUMMARY Serum gastrin was determined in 33 patients during treatment with the proton pump inhibitor omeprazole. After 4 weeks of therapy, gastrin levels increased to a median of 55 pg/ml compared to 15 pg/ml prior to omeprazole ( P < 0.001). There was a close correlation ( r = 0.939; P < 0.001) between pre‐treatment gastrin and levels at 4 weeks. Comparison of serum gastrin concentrations at I month of omeprazole with levels at 6 ( n = 21) and 12 months ( n = 12) continuous therapy revealed a close correlation ( r = 0.961 and r = 0.882, respectively; P < 0.001) despite dose adjustment. In marked hypochlorhydria documented by continuous pH monitoring, serum gastrin varied from normal up to profound hypergastrinaemia. These results demonstrate that the serum gastrin increase under powerful acid‐inhibitory drug therapy depends upon a number of variables. (a) Only in patients with elevated gastrin levels, prior to omeprazole treatment, can moderate to marked hypergastrinaemia during omperazole be expected. (b) Gastrin increases reached during the initial period of omeprazole treatment remain constant during long‐term therapy. (c) Acid inhibition itself is not necessarily associated with an increase in serum gastrin in every patient, which suggests that the individual sensitivity of the gastrin cell to acid inhibition is more important for serum gastrin changes than the degree of acid inhibition itself.
Gastrointestinal hormone
Cite
Citations (70)
Summary In a multicentre trial, 13 cannulated horses were treated orally once daily with a paste that delivered omeprazole at a dose of 4 and 5 mg/kg bwt in a 2‐period crossover design to evaluate steady state gastric acid suppression. In each period, basal (unstimulated) and pentagastrin‐stimulated gastric output were evaluated at 5–8 h after 5 doses, at 13–16 h after 10 doses, and at 21–24 h after 15 doses. Baseline data for gastric acid secretion were collected once for each horse in the month prior to initiation of omeprazole treatment. The inhibition of gastric acid secretion relative to baseline values, following treatment with omeprazole, were calculated and expressed as per cent. Pharmacokinetic data were also collected in this trial. At 4 mg/kg bwt, the oral paste formulation of omeprazole inhibited both basal and pentagastrin‐stimulated gastric acid secretion by 99% at 5–8 h after treatment and by 83% (basal) and 90% (pentagastrin‐stimulated) at 21–24 h. Inhibition following the administration of omeprazole at a dose of 5 mg/kg bwt was not significantly greater than when given at 4 mg/kg bwt. The results from this study could possibly lead to the development of an effective and practical antisecretory treatment of ulcer disease in horses.
Pentagastrin
Crossover study
Basal (medicine)
Cite
Citations (81)