Bombesin-like immunoreactivity in the pituitary gland

Summary Bombesin has been shown to stimulate release of anterior pituitary hormones both in vivo and in vitro. The aim of this study was to determine whether bombesin-like immunoreactivity could be detected in the human pituitary. Significant concentrations were found in the human anterior gland (4.6±1.5 pmoles/g), posterior gland (1.5±0.4 pmoles/g) and stalk (8.1±0.8 pmoles/g). Significant amounts were also observed in the guinea-pig pituitary. Gel permeation chromatography revealed the presence of 2 major molecular forms of bombesin-like immunoreactivity, one co-eluting with porcine gastrin-releasing peptide and the other with amphibian bombesin.     

Presence of "pancreatic polypeptide" cells, and gastrin immunoreactivity in immuno-induced exocrine pancreas carcinoma]

1) In electively immuno-induced carcinomas of the exocrine pancrease in Mice, where A (glucagon) and B (insulin) endocrine cells persist, cells with a pancreatic polypeptide immunoreactivity are also detected, even in late evolution stages. These cells, like D cells, containing somatostatin, are localized only in the pancreatic remains surrounding the anaplasic carcinomatous tissue: islets, adenomatous parenchyma, and ductular epithelium. Ultrastructure of these cells shows their active elaboration of numerous chracteristic secretion granules. (2) Immunocytoenzymatic detection of gastrin is negative in the exocrine and endocrine pancreatic tissues. However one of the anti-gastrin sera used gives a positive reaction, in some carinomatous cells only. Does this immunoreactivity characterize a polypeptide specific to the pancreatic carcinomatous cell?     

The islet-acinar axis of the pancreas: Is there a role for glucagon or a glucagon-like peptide?

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.     

Bombesin-like immunoreactivity in the pituitary gland

Bombesin has been shown to stimulate release of anterior pituitary hormones both in vivo and in vitro. The aim of this study was to determine whether bombesin-like immunoreactivity could be detected in the human pituitary. Significant concentrations were found in the human anterior gland (4.6 +/- 1.5 pmoles/g), posterior gland (1.5 +/- 0.4 pmoles/g) and stalk (8.1 +/- 0.8 pmoles/g). Significant amounts were also observed in the guinea-pig pituitary. Gel permeation chromatography revealed the presence of 2 major molecular forms of bombesin-like immunoreactivity, one co-eluting with porcine gastrin-releasing peptide and the other with amphibian bombesin.     

The influence of different nutrients on plasma cholecystokinin levels in the rat

Summary Isocaloric and isovolemic amounts of protein (casein), fat (intralipid) and carbohydrate (saccharose) and an isovolemic control solution of water were administered intragastrically to conscious rats. The plasma CCK levels, determined by a sensitive and specific radioimmunoassay, showed an increment of 6.3±0.6, 2.7±0.5, 1.7±0.4 and –0.9±0.4 pM, respectively (basal value 2.5±0.3 pM). The threshold increment of plasma CCK to stimulate pancreatic enzyme secretion by exogenous CCK was found to be 1.5 pM. It is therefore concluded that casein is a potent stimulus for CCK secretion and pancreatic secretion, but that fat and even carbohydrate, although less potent, also produce a CCK increment above the threshold for pancreatic secretion.Supported by Grant IKW 86-16 from the Netherlands Cancer Foundation KWF.     

Elective induction in mice of solid and ascitic carcinoma of the exocrine pancreas by the repeated doses of antibodies against a lipoprotein lipase fraction]

Small doses, repeated for months of anti-esterase-lipoprotein antibodies, from several antisera raised against a crude lipoprotein-lipase from Rabbit adipose tissue (2), induce exocrine pancreatic carcinomas in mice, without any specific barrier. This seems to be the first case of a quite elective carcinogenic process of the pancreas, by an immunological mechanism, with a very high incidence, up to 100%. Such carcinomas are highly metastatic, produce a pancreatic carcinomatous ascites, and are deadly. This immunological pathogeny is discussed., more particulary on an action of immuno-complexes in an abnormal physiological environment.     

Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat

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.     

An immunoreactive peptide in milk contains bombesin-like bioactivity

Summary Parallel in vitro biassays using rat uterus and guinea pig large intestine tissues specific for the bombesin family of peptides, demonstrated that the bombesin-like peptides present in bovine milk can produce a dose-related response similar to bombesin and litorin. The bioactivity of this type of milk peptide appeared to be approximately 20–50% as active as the amphibian peptides. These data support the proposal that a bombesin immunoreactive peptide in milk contains bombesin bioactivity.supported in part by a NATO Fellowship and by the Fogarty International Center of the National Institutes of Health, Bethesda, MD, USA.supported by a grant from the Consiglio Nazionale delle Ricerche     

NDRG2 is highly expressed in pancreatic β cells and involved in protection against lipotoxicity

The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell differentiation and apoptosis, but its function in the pancreas remains to be established. Herein we examine the expression and function of NDRG2 in the endocrine pancreas. NDRG2 immunoreactivity was localized mainly in the cytoplasm of pancreatic β cells. When β-TC3 cells were exposed chronically to high levels of free fatty acid (FFA), cell viability was impaired, and Akt and NDRG2 phosphorylation were reduced. NDRG2 is a potential substrate of protein kinase Akt. Overexpression of constitutively active Akt enhanced NDRG2 phosphorylation and abolished the apoptosis induced by FFA in β-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of β cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic β cells and is involved in the Akt-mediated protection of β cells against lipotoxicity.     

Effect of pancreatic polypeptide on DNA-synthesis in the pancreas

Summary Bovine pancreatic polypeptide increases DNA-synthesis in the rat pancreas; no effect is observed in stomach (oxyntic area), duodenum or liver. BPP neither augments or inhibits the trophic action of cholecystokinin.Acknowledgment. Pure pancreatic polypeptide was donated by Dr. R. E. Chance (Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind, USA). G. R. Greenberg is supported by a Fellowship of the Medical Research Council of Canada.     

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.     

Preliminary observations on the co-existence of regulatory peptides in cells of the baboon endocrine pancreas

Summary Immunocytochemical procedures at ultrastructural and light microscopy level revealed, in the Chacma baboon endocrine pancreas, cells which were immunoreactive for glucagon and pancreatic polypeptide (PP). Some D cells were observed to contain secretory granules with both the appearance and immunoreactivity of A cell secretory granules.     

Preliminary observations on the co-existence of regulatory peptides in cells of the baboon endocrine pancreas

Immunocytochemical procedures at ultrastructural and light microscopy level revealed, in the Chacma baboon endocrine pancreas, cells which were immunoreactive for glucagon and pancreatic polypeptide (PP). Some D cells were observed to contain secretory granules with both the appearance and immunoreactivity of A cell secretory granules.     

Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells

In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.     

New approaches to therapy of cancers of the stomach,colon and pancreas based on peptide analogs

Cancers of the stomach, colon and exocrine pancreas are major international health problems and result in more than a million deaths worldwide each year. The therapies for these malignancies must be improved. The effects of gastrointestinal (GI) hormonal peptides and endogenous growth factors on these cancers were reviewed. Some GI peptides, including gastrin and gastrin-releasing peptide (GRP) (mammalian bombesin), appear to be involved in the growth of neoplasms of the GI tract. Certain growth factors such as insulin-like growth factor (IGF)-I, IGF-II and epidermal growth factor and their receptors that regulate cell proliferation are also implicated in the development and progression of GI cancers. Experimental investigations on gastric, colorectal and pancreatic cancers with analogs of somatostatin, antagonists of bombesin/GRP, antagonists of growth hormone-releasing hormone as well as cytotoxic peptides that can be targeted to peptide receptors on tumors were summarized. Clinical trials on peptide analogs in patients with gastric, colorectal and pancreatic cancers were reviewed and analyzed. It may be possible to develop new approaches to hormonal therapy of GI malignancies based on various peptide analogs.Received 20 November 2003; accepted 6 January 2004     

Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells

Summary In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.     

Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat

Summary 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 g/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.     

Demonstration of tissue-specific antigens shared by normal pancreas and pancreatic neoplasms

Summary Xenoantiserum raised against extracts of normal hamster pancreas, after absorption with normal tissues, reacted specifically with normal hamster and human pancreas by immunodiffusion. Absorbed antiserum also reacted with hamster and human pancreatic carcinoma but not with other neoplasms. Immunization of hamsters with normal pancreas extracts prevented growth of transplantable pancreatic carcinomas.     

Demonstration of tissue-specific antigens shared by normal pancreas and pancreatic neoplasms

Xenoantiserum raised against extracts of normal hamster pancreas, after absorption with normal tissues, reacted specifically with normal hamster and human pancreas by immunodiffusion. Absorbed antiserum also reacted with hamster and human pancreatic carcinoma but not with other neoplasms. Immunization of hamsters with normal pancreas extracts prevented growth of transplantable pancreatic carcinomas.     

Über eine selektive Mitosehemmung und -schädigung bei jungen Ratten durch Synthalin A

Summary A single subcutaneous injection of synthalin-A does not affect the cytoplasma ofA-cells in pancreatic islets of the rat during the 1^st–5^th day of life, in contrast to adult animals. Selective action was found on mitoticA-cells: reduction of mitotic frequency to 25% of the normal rate, and pathological mitoses in the sense of the so-called primary effect. The mitoses ofB-cells, exocrine pancreatic cells and intestinal epithelia seemed to be unchanged, although the mitotic rate was higher than inA-cells.