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PubMed1992

Peptide maps of five human pepsin isoenzymes and other aspartic proteinases.

Peptide maps of five individual human pepsins were developed using reversed-phase high-performance liquid chromatography after protein digestion with either Staphylococcus aureus proteinase (V8) or alpha-chymotrypsin. Human pepsins 3a, 3b and 3c produced almost identical peptide maps suggestive of proteins with very similar amino acid sequences. The map for human pepsin 1 was similar to pepsin 3b (the most predominant human pepsin) but less than half the expected amount of each equivalent peptide fragment was generated, indicating that the actual mass of digested protein used was less than the dry weight measurement would suggest, probably as a result of carbohydrate attached to pepsin 1. Comparison of human pepsin 3b maps with other aspartic proteinases confirmed a significant homology with swine pepsin A but not with endothiapepsin. The alpha-chymotrypsin digests compared with V8 gave more complex peptide maps as a result of its broader bond cleavage specificities.

Animals↗

PubMed1983

Purification and characterization of pepsins from the arctic fish capelin (Mallotus villosus).

Two pepsins from the stomach of the arctic fish capelin (Mallotus villosus) have been isolated and characterized. The purification was achieved by ammonium sulphate precipitation, ion exchange chromatography and gel filtration. Both pepsins resemble mammalian pepsins regarding pepstatin sensitivity, amino acid composition, stability and specific activity. The major capelin pepsin has optimum activity at significantly higher pH than is common for mammalian pepsins, and the optimum pH is different with different substrates. Both pepsins have relatively high activity at low temperatures. The pepsins have mol. wt of about 25,000 which is significantly lower than that of mammalian pepsins.

Amino Acids↗

PubMed1982

Comparison of pepsins isolated from porcine, bovine and Penicillium jathiuellum.

1. The reactivities of pepsins, isolated from three different sources (porcine, bovine, and Penicillium jathiuelum), toward ester and peptide substrates were compared. 2. Porcine pepsin showed the highest activity followed by penicillopepsin with bovine pepsin being the least active. 3. The esterase activity of penicillopepsin was greater than that of porcine pepsin with bovine pepsin again showing the least activity. 4. The CD spectra indicate that porcine and bovine pepsin have similar conformations, even though bovine pepsin shows less ellipticity at 220 nm. 5. Penicillopepsin showed a completely opposite sign in the near-u.v. region of the CD spectrum. 6. The far-u.v. region of the CD spectrum of penicillopepsin strongly suggests a beta-sheet structure. 7. Previously reported X-ray crystallographic data suggest that porcine pepsin has a compact three-dimensional structure, while the structures of bovine and penicillopepsins are partially unfolded.

Amino Acids↗

PubMed1984

Pepsin-immunoregulation hypothesis.

Pepsin exists in macrophages. Phagocytosis of foreign materials increases pepsin activity in macrophages and also causes extracellular release of pepsin from macrophages. Pepsin enhances antibody production by spleen cells against heterologous materials and suppresses that against homologous materials. Pepsin selectively decomposes immune complexes at neutral pH, and intravenous pepsin ameliorates symptoms in autoimmune disease models, such as immune complex glomerulonephritis in MRL/l mice and SLE-like syndromes of NZB/W F1 mice. These results prompted us to propose a "pepsin-immunoregulation hypothesis", according to which pepsin acts as a regulating factor in the immune system.

Animals↗

PubMed1999

Pepsin-digested peanut contains T-cell epitopes but no IgE epitopes.

BACKGROUND: Peanuts are a common cause of food-induced anaphylaxis and fatalities. Previous studies have demonstrated that rush immunotherapy to crude peanut extract reduces clinical symptoms triggered by oral peanut challenges, but the immunotherapy was associated with an unacceptably high incidence of systemic allergic reactions. One approach to reduce the frequency of allergic reactions would be to use a modified peanut antigen with low allergenic properties. OBJECTIVE: We sought to determine the immunologic characteristics of crude intact peanut extract before and after pepsin digestion. METHODS: We used IgE immunoblotting and assessment of T-lymphocyte responses to intact and peptic digests of peanut extracts. RESULTS: Western blot analysis of sera from 5 subjects with peanut allergy showed multiple IgE-reactive proteins in crude intact peanut extract that were eliminated after pepsin treatment of the peanut extract. In contrast, pepsin-digested peanut induced significant T-cell proliferation responses (stimulation index = 30) in vitro in PBMCs from 7 subjects with peanut allergy, albeit at lower levels than that induced by intact peanut (stimulation index = 66). Furthermore, IFN-gamma production was induced by intact peanut and pepsin-digested peanut in a concentration-dependent manner. Importantly, T-cell lines generated in response to intact peanut also reacted to pepsin-digested peanut, indicating cross-reactive T-cell epitopes in intact and pepsin-digested peanut. CONCLUSION: These findings suggest that pepsin-digested peanut may be useful in peanut immunotherapy because pepsin digestion eliminates IgE reactivity but maintains T-cell reactivity.

Adult↗

PubMed2004

Integration of on-line protein digestion, peptide separation, and protein identification using pepsin-coated photopolymerized sol-gel columns and capillary electrophoresis/mass spectrometry.

A miniaturized pepsin reactor was prepared inside a fused-silica capillary (i.d. 75 microm) by coating a pepsin-containing gel on a photopolymerized porous silica monolith. The pepsin-encapsulated film was prepared by a sol-gel method. The sol-gel reaction was optimized so that the sol solution containing pepsin forms a thin film on the photopolymerized sol-gel (PSG) monolith that was initially fabricated at the inlet of the capillary. Pepsin was encapsulated into the gel matrix without losing its activity. The large surface area of the PSG monolith enabled the immobilized pepsin to achieve a high catalytic turnover rate, and the porous nature of the PSG promotes penetration of large molecular proteins into the column. The immobilized pepsin-digested peptides and proteins, and the resulting mixture of peptide fragments, could be directly separated in the portion of the capillary where no PSG monolith exists. The durability and repeatability of the fabricated pepsin-coated column was tested and found to be satisfactory. An acidic solution consisting of 0.5 M formic acid was used as the running buffer, because it suppresses the adsorption of proteins or peptides on the inner surface of the capillary as well as enables direct connection of the output of the capillary electrophoresis column to a mass spectrometer. The on-line digestion of insulin chain beta and lysozyme provides identification of the proteolytic peptides. Recovery was achieved for 100% of the insulin chain beta amino acid sequence and 73% of the lysozyme amino acid sequence.

Amino Acid Sequence↗

PubMed1977

Improved pepsin inhibitor derived from activation peptide 1-16 of porcine pepsinogen.

The peptide Leu-Val-Lys-Val-Pro-Leu-Val-Arg-Lys-Lys-Ser-Leu-Arg-Gln-Asn-Leu, a known pepsin inhibitor, is derived from the first 16 amino acids of porcine pepsinogen. It was prepared from the activation mixture and was modified by guanidination of its three lysine residues to form homoarginine residues. The modified peptide is a better pepsin inhibitor than the native peptide; for 50% inhibition of the milk clotting action of pepsin at pH 5.3, the molar ratio of peptide to pepsin required is 9 for the native inhibitor and only 2 for the guanidinated inhibitor. The dissociation constants (k1) of the inhibitor-pepsin complexes are 7 X 10(-8) and 1.4 X 10(-8) M for the native and guanidinated peptides, respectively. The guanidinated peptide is more resistant to digestion by pepsin at pH 3.5. The native and modified peptides partially protect pepsin from inactivation at pH 7. Stepwise removal of the amino-terminal Leu-Val-Har residues from the guanidinated inhibitor by Edman degradation decreases the pepsin-inhibiting activity only slightly at the first step, but markedly at the second and third steps. Thus, all of the amino-terminal sequence except the leucine residue is necessary for full activity.

Amino Acids↗

PubMed2004

Role of S'1 loop residues in the substrate specificities of pepsin A and chymosin.

Proteolytic specificities of human pepsin A and monkey chymosin were investigated with a variety of oligopeptides as substrates. Human pepsin A had a strict preference for hydrophobic/aromatic residues at P'1, while monkey chymosin showed a diversified preferences accommodating charged residues as well as hydrophobic/aromatic ones. A comparison of residues forming the S'1 subsite between mammalian pepsins A and chymosins demonstrated the presence of conservative residues including Tyr(189), Ile(213), and Ile(300) and group-specific residues in the 289-299 loop region near the C terminus. The group-specific residues consisted of hydrophobic residues in pepsin A (Met(289), Leu/Ile/Val(291), and Leu(298)) and charged or polar residues in chymosins (Asp/Glu(289) and Gln/His/Lys(298)). Because the residues in the loop appeared to be involved in the unique specificities of respective types of enzymes, site-directed mutagenesis was undertaken to replace pepsin-A-specific residues by chymosin-specific ones and vice versa. A yeast expression vector for glutathione-S-transferase fusion protein was newly developed for expression of mutant proteins. The specificities of pepsin-A mutants could be successfully altered to the chymosin-like preference and those of chymosin mutants, to pepsin-like specificities, confirming residues in the S'1 loop to be essential for unique proteolytic properties of the enzymes. An increase in preference for charged residues at P'1 in pepsin-A mutants might have been due to an increase in the hydrogen-bonding interactions. In chymosin mutants, the reverse is possible. The changes in the catalytic efficiency for peptides having charged residues at P'1 were dominated by k(cat) rather than K(m) values.

Amino Acid Sequence↗

PubMed1988

Inhibition of porcine pepsin by two substrate analogues containing statine. The effect of histidine at the P2 subsite on the inhibition of aspartic proteinases.

Two new inhibitors, 4 and 5, of the aspartic proteinase porcine pepsin were synthesized. These compounds, which span the P4-P'3 binding subsites of the enzyme, were derived by replacing the Nph-Phe dipeptidyl unit of a good pepsin substrate, H2N-Phe-Gly-His-Nph-Phe-Ala-Phe-OMe (3), with statine [(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, Sta]. Hexapeptide 5, H2N-Phe-Gly-Val-(S,S)-Sta-Ala-Phe-OMe, is an extremely potent inhibitor of pepsin with a Ki value less than 1 nM. This result is consistent with the proposal that statine functions as a bioisosteric replacement for a substrate dipeptidyl unit. Compound 4, which contains His at P2, is 2 orders of magnitude less active than the valine analogue 5 (Ki = 150 nM). The factor for the decrease in binding to pepsin effected by replacement of Val by His at P2 parallels the ratio of protonated vs unprotonated imidazole group in peptide 4 at pH 4, according to the Henderson-Hasselbach equation. This result suggests that a positively charged side chain at P2 is undesirable for maximum pepsin inhibition. Kinetic constants for several known inhibitors of pepsin and renin are presented that demonstrate that the effect of His incorporation at P2 on pepsin inhibition depends upon the peptide sequence and that the effect is considerably different for renin inhibitors. We further suggest that the high selectivity of potent renin inhibitors known to be only weak pepsin and cathepsin D inhibitors is due in part to the extent of histidine protonation at P2 arising from pH differences in the inhibition kinetics assay of renin (neutral conditions) compared to other aspartic proteinases (acid pH 2-4).

Algorithms↗

PubMed1976

Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin.

1. A fragment of human subcomponent C1q was prepared by limited proteolysis with pepsin at 37 degrees C for 20 h, and at pH4.4, followed by gel filtration on Sephadex G-200. This fragment was shown to contain all the collagen-like features known to be present in the intact molecule [Reid (1976) Biochem. J. 155, 5-17]. 2. Circular-dichroism studies showed the presence of positive bands at 230 and 223 nm in the intact subcomponent C1q and pepsin fragment respectively, compared with a positive band at 220 nm obtained for lathyritic rat skin collagen. These bands were abolished by collagenase treatment, which suggested that there may some collagen-like triple-helical structure in subcomponent C1q and that this structure resides in the pepsin-resistant portion of the molecule. However, the 230 and 223 nm bands had a substantially lower magnitude than that obtained for the unaggregated single fibres of totally triple-helical collagen. 3. Thermal-transition temperatures obtained for subcomponent C1q, the pepsin fragment and the reduced and alkylated pepsin fragment were 48 degrees, 48 degrees and 39 degrees C respectively, compared with a value of 38 degrees C obtained for lathyritic rat skin collagen. 4. Only the unreduced pepsin fragment regained significant amounts (up to 60%) of collagen-like structure, after heat denaturation and cooling, as estimated by circular-dichroism measurements. 5. Electron-microscopy studies of subcomponent C1q and the collagen-like pepsin-resistant fragment of subcomponent C1q showed that the six peripheral globular regions of the molecule were fragmented by pepsin leaving the six collagen-like connecting strands and fibril-like central portion intact.

Animals↗

PubMed1999

Ecabet sodium, a novel locally-acting anti-ulcer agent, protects the integrity of the gastric mucosal gel layer from pepsin-induced disruption in the rat.

BACKGROUND: Ecabet sodium, a novel non-systemic anti-ulcer agent, possesses high affinity to gastric adherent mucus, which plays an important role in the protection of the gastric epithelium against acid and pepsin. AIM: To assess the effect of ecabet on pepsin-induced degradation of the structure of the mucus gel layer. METHODS: Everted sacs of rat stomach were incubated in HCl solution containing pepsin with or without ecabet. Pepsin-induced release of the cleaved peptides and hexosamine from the sacs was determined. Changes in the molecular size of glycoproteins in the adherent mucus (using gel filtration methods) and in the morphology of the epithelium (using both light and scanning electron microscopy) were also examined. RESULTS: Ecabet reduced the pepsin-induced release of peptides and hexosamine, depending on its content in the adherent mucus. Pepsin treatment partially lowered the molecular weight of native glycoproteins in the adherent mucus, caused exfoliation of the epithelial cells, and degraded the network-like ultrastructure of the mucus layer, giving it a lumpy, globular appearance. Ecabet prevented both the pepsin-induced molecular size shift in mucus glycoproteins, and morphological alteration of the epithelium, including ultrastructural derangement of the mucus gel layer. CONCLUSION: Ecabet protects the polymeric structure of mucus glycoproteins from proteolytic degradation by pepsin, and thus maintains integrity of the gastric mucus gel layer.

Abietanes↗

PubMed1976

A comparison of the pepsin stimulating effects of secretin preparations.

1. The peptic responses to Boots, GIH and synthetic secretins have been compared in fasting anaesthetized cats in which the pylorus and bile duct were occluded to prevent the release of duodenal hormones by acid and bile salts. A quantity of dilute acid introduced into the stomach at regular intervals ensured the total recovery of viscid secretions and preserved peptic activity. 2. The mean peak outputs of pepsin obtained in response to Boots secretin were significantly greater than the mean peak outputs of pepsin stimulated by equipotent doses of GIH secretin (4 Crick-Harper-Raper units of Boots secretin have been shown to stimulate a flow of juice and bicarbonate from the pancreas equal to that produced by 1 clinical unit of GIH secretin). The maximum output of pepsin stimulated by Boots secretin, 16 C.H.R. u./kg hr was 3 times the observed maximum output in response to the 4 times more potent dose of GIH secretin, 16 c.u./kg hr. The slopes of the log dose-response lines were significantly different for these two products indicating that their modes of action in stimulating pepsin may not be identical. 3. The outputs of pepsin following GIH and synthetic secretin were similar. Both these secretins stimulated the secretion of pepsin when infused in doses which stimulated the pancreas supramaximally. The less pure product Boots secretin evoked significantly higher peptic responses at doses submaximal for pancreatic stimulation, suggesting that a substance other than secretin exists in Boots preparations which contributes significantly to the overall output of pepsin in response to this product. The peptic response which was accompanied by a slight increase in acid output, but without any increase in pancreatic lipolytic activity, was not inhibited by atropine. This substance which is not present in highly purified GIH secretin does not appear to be cholic acid, gastrin, pancreozymin, glucagon or insulin. 4. The possibility that a vasodilator substance is present in Boots secretin which by expanding the splanchnic bed increases the concentration of secretin at target sites in the stomach and pancreas seems unlikely, as the flow of pancreatic juice does not increase proportionately with the vast increase in pepsin. A vasodilator substance which specifically affects the gastric vasculature remains a theoretical but unlikely explanation for our observation.

Animals↗

PubMed1993

Assay of gastricsin and individual pepsins in human gastric juice.

AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.

Chromatography, Ion Exchange↗

PubMed2005

Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts.

BACKGROUND: A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR. METHODS: Standardised 3 x 60 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls. RESULTS: Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels. CONCLUSION: These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.

Adult↗

PubMed1984

Dissociated response of acid and pepsin secretion to omeprazole in an in vitro perfused mouse stomach.

The effect of omeprazole, an inhibitor of the parietal cell H+-K+-ATPase, on pepsin and acid secretion was studied in an in vitro perfused whole mouse stomach model. Omeprazole inhibited basal and dibutyryl cAMP (DBcAMP)- and histamine-stimulated acid secretion in a dose-dependent fashion with a maximally effective dose of 10(-4) M. At the same time, omeprazole induced a dose-dependent increase of unstimulated pepsin release. This increase was not affected by pretreatment with 10(-3) M atropine or 10(-4) M cimetidine. It was, however, inhibited by preincubation with 10(-4) M carbonyl cyanide m-chlorophenylhydrazone (CCCP). Pepsin secretion after maximally effective doses of histamine or DBcAMP was not affected by 10(-4) M omeprazole. In a concentration of 10(-5) M, the effect of omeprazole was additive to the effect of submaximal concentrations of carbachol and histamine. NaSCN and imidazole mimicked the effect of omeprazole on acid secretion, but pepsin release was only stimulated with 10(-2) M imidazole. Another weak base, benzylamine, stimulated acid and pepsin in parallel. Luminal perfusion with solutions of high K+ concentration did not enhance basal pepsin release. The dissociated response of acid and pepsin secretion indicates that omeprazole does not act selectively on the parietal cell. The stimulation of pepsin secretion might be related to the weak base properties of the compound.

Animals↗

PubMedDate not supplied

Detection of pepsin in tracheal secretions after forced small-volume aspirations of gastric juice.

BACKGROUND: Detecting small-volume aspirations of gastric contents is an important but difficult task. A potentially useful method for this purpose is assaying tracheal secretions for pepsin, an expected constituent of gastric juice. METHODS: A 2-group experimental design was used. The primary subjects were 161 experimental and 21 control New Zealand white rabbits; 161 acutely ill humans provided the gastric juice used in the project. The animals were anesthetized before being intubated and mechanically ventilated. Three separate boluses of human gastric juice mixed with dye-stained enteral formula were instilled into the experimental animals' tracheas; the 21 control animals received only 0.9% sodium chloride solution. At the beginning of each experiment, 0.4 mL/kg of the substance was infused over a 30-minute period; the infusion was then stopped and 90 minutes were allowed to elapse before endotracheal suctioning was performed. This procedure was repeated at hour 2 and hour 4. After completion of the multiple aspiration portion of the study, 23 additional animals were subjected to a single aspiration of 0.4 mL/kg of a mixture of human gastric juice and dye-stained enteral formula; secretions were obtained at 2 hours, 4 hours, and 6 hours. An immunoassay was used to test for pepsin in all of the tracheal secretions. RESULTS: In the 3-aspiration group, pepsin was found in all of the secretions from 92.5% (149/161) of the experimental animals; in contrast, no pepsin was found in any of the secretions from the 20 control animals. In the single-aspiration group, pepsin was found in all of the tracheal secretions from the 23 animals at 2 hours and 4 hours and 21 of the 23 animals at 6 hours. CONCLUSIONS: The immunoassay used in this animal model study was able to detect pepsin in >90% of the experimental animals' tracheal secretions after multiple or single forced aspirations of gastric juice. The extent to which pepsin can be detected in the tracheal secretions of acutely ill tube-fed humans requires investigation, as does the extent to which clinical outcomes are affected by pepsin-positive tracheal secretions.

Animals↗

PubMed1980

Secretion of pepsins and hydrogen ions in the stomach of children undergoing cardiac surgery.

Gastric juice was collected from 27 children for 9 to 21 hr following cardiac surgery, from 4 further children during and following cardiac surgery, and from 3 children who had not undergone surgery. Each sample was analyzed for hydrogen ion and pepsin content. The pH of the postoperative secretions from 26 patients was 1.25 to 5.30, and the mean hydrogen ion concentration was 60.1 mmol/liter (range, 21.5 to 119.3 mmol/liter). The mean peptic activity (83.0 units/ml; range, 42.4 to 158.4 units/ml) was not age related and was significantly higher than that of the basal and pentagastrin-stimulated secretion and similar to that of vagally stimulated secretion of adults with peptic ulcer. The pepsin:hydrogen ion and pepsin 1:total pepsin ratios also resembled those of vagally stimulated secretion. During the first 90 min of cardiac surgery, the pH of aspirated gastric juice was 1.40 to 4.90, the hydrogen ion concentration was 15.8 to 72.3 mmol/liter, peptic activity was 39.2 to 164.0 units/ml (mean, 97.2 units/ml). Pepsin 1 was present in all samples. Aspirates from 3 unoperated children had low total peptic activity and only trace amounts of pepsin 1. Children from the age of 5.5 months thus have the capacity to secrete all the major pepsins, including pepsin 1. The findings suggest that vagal stimulation of gastric secretion was occurring during the postoperative period.

Adolescent↗

PubMed1987

Pepsin secretion by the totally isolated, vascularly perfused rat stomach.

The gastric pepsin output by the totally isolated, vagally denervated, and both luminally and vascularly perfused rat stomach was studied. Basal release of pepsin was 3% of total gastric mucosal stores per hour. Topical (luminal) administration of 0.001 M HCl was without effect. Graded concentrations of pentagastrin, gastrin, histamine, and impromidine in the vascular perfusate were tested. Pentagastrin induced only a slight increase in pepsin release (15% of total content per hour). Gastrin had a more pronounced effect and elicited a significant increase in the pepsin output, reaching a maximum of 28% of total pepsin content per hour. The CD50 of gastrin was 0.061 nM. Histamine and impromidine likewise produced significant increases in the pepsin secretion (maximum, 40% and 35% of total stores per hour, respectively). When the CD50 of histamine (0.718 microM) was compared with that of impromidine (0.011 microM), impromidine on molar basis had 65 times higher potency than histamine as a pepsin secretagogue. When the pepsin and acid responses during gastrin, histamine, and impromidine stimulation were compared, the pepsinogen secretion was shifted to the left and thus was more sensitive to stimulation than the acid secretion.

Animals↗