Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigates the inhibitory effect of the novel potent benzodiazepine-related CCK-antagonist L-364,718 on pancreatic growth in the rat induced by chronic administration of caerulein and bombesin-like peptides. Caerulein, injected s.c. twice daily at a dose of 1 microgram/kg body weight, and bombesin (10 micrograms/kg) induced a similar increase (1.5-3-fold) in pancreatic wet weight, total protein, amylase, trypsin, putrescine and spermidine content after 14 days of treatment. Growth induced by caerulein showed a significant increase in total DNA content suggesting cellular hyperplasia, whereas bombesin-like peptides led to cellular hypertrophy. In comparison to bombesin the decapeptide neuromedin C (10 micrograms/kg) was found to be 30-50% less potent. In the same dose range, neuromedin B and the tachykinins neurokinin A and B, all structurally related to bombesin, had no significant trophic effect on the rat pancreas. Administration of the CCK-antagonist L-364,718 twice daily at a dose of 0.1 mg/kg or at 1.0 mg/kg, either s.c. or orally, led dose-dependently to a near-complete inhibition of the caerulein-induced trophic effect. In contrast, L-364,718 administered at identical dosages, did not affect pancreatic hypertrophy induced by bombesin and neuromedin C. It is concluded that both peptides mediate their effect on the rat pancreas directly and not via release of endogenous cholecystokinin. Tachykinins are not involved in the regulation of pancreatic growth. Caerulein- and bombesin-like peptides have comparable effects on the stimulation of protein and polyamine synthesis.
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PMID:CCK-antagonist L-364,718: influence on rat pancreatic growth induced by caerulein and bombesin-like peptides. 254 30

Because of the presence of bombesin-like immunoreactivity in milk, we investigated if enteral administration of bombesin affects the intestinal luminal content of trypsin and protein in 12-14-day-old rats. Bombesin (40 micrograms/kg), given either orogastrically or subcutaneously, produced a significant elevation in the intestinal content of trypsin activity. Thus, enterally-administered bombesin can produce acute biologic effects in suckling rats.
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PMID:Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat. 270 78

The immediate postnatal period is a time of rapid pancreatic growth and development. Gastrointestinal regulatory peptides have been shown to exert trophic effects on the pancreas, and one such peptide, bombesin, has been shown to exert trophic effects on the pancreas of both the suckling and adult rat. Our previous studies had suggested that the sensitivity of the rat pancreas to bombesin might be changing during the suckling period. We therefore conducted experiments to determine if age-related changes in the responsiveness of rat pancreas to chronic administration of exogenous bombesin occur, and to characterize these changes. Beginning on day 3 ("suckling") or 24 ("weanling") postnatally, groups of rats were injected subcutaneously with several doses of bombesin tetradecapeptide every 12 h for 7 days. Bombesin injection produced a dose-dependent increase in pancreatic protein content and trypsin activity in both suckling and weanling groups, although the degree of increase was greater in the weanling group than in the sucklings. Significant increases in pancreatic contents of DNA and amylase activity were observed only in the weanling group. We have thus demonstrated for the first time that the pancreas of the suckling rat exhibits a diminished response to chronic parenteral administration of bombesin in terms of changes in protein and DNA contents, as well as enzyme composition, compared to the pancreas of weanlings. The elucidation of the physiologic basis for these differences may provide specific information regarding the mechanism of bombesin-stimulated pancreatic growth, as well as general information concerning the control of pancreatic growth during development.
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PMID:Age and enzyme specificity of the response of developing rat pancreas to the trophic effects of bombesin. 271 99

We examined the effects of several in vitro experimental systems on the apparent potencies of putative secretagogues for stimulating ACTH release from rat anterior pituitary cells. Cells were prepared by trypsin digestion and gentle mechanical dispersion. Aliquots of the same cell preparations were tested in 1) a microperifusion system immediately after dispersion (day 0), 2) the same microperifusion system after 4 days of static suspension culture on a layer of Sephadex G-10 gel particles (day 4), 3) a static suspension system after 4 days of static suspension culture, and 4) a static monolayer system after 4 days of monolayer culture. Ovine CRF stimulated release of similar amounts of ACTH in all of the systems on days 0 and 4, except in one experiment, in which the response was less on day 4. Arginine vasopressin (AVP), oxytocin, and angiotensin II all appeared to be more potent in day 4 than in day 0 cells in the perifusion system, and the synergism of AVP with ovine CRF was also increased. Dioctanoylglycerol, which directly activates protein kinase-C, and forskolin, which directly activates adenylate cyclase, both stimulated greater release in day 4 cells. The mechanism(s) responsible for the difference in the responses of day 0 and day 4 cells is unknown. Epinephrine had only a small effect in the microperifusion system, but both epinephrine and norepinephrine had potencies comparable to AVP in the static suspension and monolayer systems. This was not due to prolonged exposure to the catecholamines, suggesting that these agents may act on other anterior pituitary cells to release metabolic products that secondarily stimulate the corticotrophs to release ACTH. The same situation appears to be true for atrial natriuretic factor. Gastrin-releasing peptide, its bioactive COOH-terminal half, which was active in a rat urinary bladder smooth muscle assay, its amphibian analog, bombesin, and cholecystokinin (26-33) were devoid of ACTH-releasing activity in all of the systems, in contrast to the findings of others. Since 4-day culture of dispersed cells improved most of their responses and diminished none, we postulate that they may more closely resemble normal pituitary cells in function, and since cellular metabolites are unlikely to accumulate in the interstitial fluid of the pituitary gland, we propose that the secretory functions of cells in perifusion systems may more closely resemble those in the pituitary gland in situ than they do in static incubation systems.
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PMID:Effects of several in vitro systems on the potencies of putative adrenocorticotropin secretagogues on rat anterior pituitary cells. 283 88

This study was undertaken to determine the effect of atropine and somatostatin, two inhibitors of intraduodenal pancreatic enzyme secretion, on bombesin-stimulated release of plasma immunoreactive trypsin in 6 healthy volunteers. Infusion of 5 ng/kg.min bombesin during 30 min induced significant increases in plasma trypsin from 206 +/- 20 to 334 +/- 44 ng/ml (p less than 0.01). Atropine (15 ng/kg as i.v. bolus followed by 5 ng/kg.h) had no influence on the bombesin-stimulated increase in plasma immunoreactive trypsin (207 +/- 20 to 326 +/- 54 ng/ml). Somatostatin (125 micrograms as i.v. bolus followed by 125 micrograms/h) also failed to inhibit the plasma trypsin response to bombesin (207 +/- 18 to 663 +/- 166 ng/ml). These results point to major differences in the regulation of plasma and intraduodenal trypsin secretion.
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PMID:Effect of atropine and somatostatin on bombesin-stimulated plasma immunoreactive trypsin release in man. 288 97

Binding sites in the rat forebrain were characterized using (125I-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides.
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PMID:Receptors for GRP/bombesin-like peptides in the rat forebrain. 299 40

The nature of bombesin-like immunoreactive peptides was studied in extracts of small cell carcinoma of the human lung. Three peaks, I, II and III, designated by their increasing retention times, were separated by reversed-phase high performance liquid chromatography (HPLC) with trifluoroacetic acid (TFA) as counter ion. None of the peaks corresponded to bombesin. Peak III was eluted at the same position as porcine gastrin releasing peptide (GRP) but was separated from it in another reversed-phase system using heptafluorobutyric acid (HFBA). Peak II material eluted in the position of bombesin in the HFBA system but not in the TFA system. The elution position of Peak I corresponded to that of the carboxyl terminal fragments of GRP, i.e. GRP18-27 and GRP19-27. This correspondence was observed in each of the reversed-phase and gel filtration systems used. The Peak III peptide was converted to peak I after incubation with trypsin. It was reasoned that this conversion could be one of the steps in the processing of bombesin-like peptides in human small cell carcinoma.
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PMID:Bombesin-like peptides in human small cell carcinoma of the lung. 301 57

We evaluated the behavior of serum cationic trypsinogen (SCT), an enzyme of solely pancreatic origin, in 30 patients with chronic pancreatitis and 25 healthy subjects as a control, after secretin and bombesin stimulation. After both the stimulations, serum cationic trypsinogen is unable to distinguish between the healthy control subjects and the patients with chronic pancreatitis. On the other hand, after secretin, the enzyme is able to separate chronic pancreatitis patients with different levels of exocrine function insufficiency. It does so with a greater statistical significance than that obtained by the rapid injection of bombesin and equal to that of trypsin into the duodenal juice during duodenal intubation. For these reasons, as well as the absence of any side-effects, secretin is preferred to bombesin stimulation in the evaluation of the exocrine pancreatic function in patients with chronic pancreatitis.
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PMID:Different responses of serum cationic trypsinogen to secretin and bombesin in normal subjects and patients with chronic alcoholic pancreatitis. 343 9

Since bombesin is a potent stimulus of the release of cholecystokinin (CCK), it has been suggested that the stimulatory effect of bombesin on pancreatic enzyme secretion is mediated by CCK. The present study was undertaken to determine the role of CCK in the bombesin-induced stimulation of plasma immunoreactive trypsin. Plasma CCK was measured by radioimmunoassay using the antibody T204, which binds to all biologically active sulfated COOH-terminal CCK-peptides. Plasma trypsin was also measured by radioimmunoassay. Infusion of 5 ng/kg/min bombesin in 6 healthy volunteers increased plasma CCK from 1.2 +/- 0.2-8.9 +/- 0.7 pM (p less than 0.0001). The peak increment in plasma CCK during bombesin (9.3 +/- 0.6 pM) was accompanied by a significant rise in plasma trypsin from 206 +/- 21-334 +/- 44 ng/ml (p less than 0.01). However, when similar increases in plasma CCK were achieved by infusion of 0.018 CU/kg/min CCK-33 (9.9 +/- 0.8 pM) or by intraduodenal instillation of 250 ml 20% Intralipid (9.7 +/- 1.9 pM), no significant changes in plasma trypsin were observed. It is therefore concluded that the stimulatory effect of bombesin on plasma immunoreactive trypsin is not mediated by CCK.
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PMID:Effect of bombesin and cholecystokinin on plasma immunoreactive trypsin in humans. 362 32

The effects of cadmium and bombesin on exocrine pancreatic secretions and plasma levels of gastrin and cholecystokinin (CCK) were studied in anesthetized rats with pancreatic and gastric fistulas. Rats treated only with saline were used as controls. Both control and cadmium (0.1 mg per kg) treated rats were infused with saline, secretin, and bombesin (BBS). Blood and pancreatic juice samples were collected at regular time intervals. Plasma levels of gastrin and CCK were measured in blood samples by specific radioimmunoassay. Pancreatic juice samples were measured for volume, protein, and trypsin outputs. Compared to saline treated rats, outputs of volume, protein, and trypsin were significantly greater in cadmium treated rats. Plasma levels of gastrin were suppressed with secretin but significantly elevated with BBS. Plasma CCK levels were not different from basal after secretin or BBS in rats treated with either cadmium or saline. The results suggest that the administration of cadmium stimulated exocrine pancreatic secretion by a mechanism that does not involve gastrin or CCK. Bombesin may have a direct influence on the stimulation of exocrine pancreatic secretion in rats.
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PMID:Effect of cadmium and bombesin on exocrine pancreatic secretions and plasma levels of gastrin and cholecystokinin (CCK) in rats. 380 Mar 2


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