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J F Rehfeld

Publications and source records attributed to J F Rehfeld.

At least 163 records · Page 9Linked to original sources
PubMed1994

The molecular nature of cholecystokinin in plasma. An in vivo immunosorption study in rabbits.

The nature of cholecystokinin (CCK) in rabbit plasma was examined by means of a novel in vivo immunosorption procedure. Cholecystokinin (CCK) antibodies in 11 rabbit antisera were denatured, and the released peptides characterized by size and reversed-phase chromatography. Five of six antisera specific for the COOH terminus of CCK contained substantial amounts of CCK-22- and CCK-8-like peptides and small amounts of CCK-33-like peptides (range, 120 to 1140 nmol/l antiserum). In contrast, neither antisera for the NH2-terminus and mid-sequence of porcine CCK-33 nor antisera against the glycine-extended COOH terminus released CCK peptides. Postprandial acidified plasma from non-immunized rabbits concentrated in vitro also contained mainly CCK-22- and -8-like peptides, whereas extracts of rabbit duodenum and jejunum in addition contained forms resembling CCK-58, -39, and/or -33. The results show that mainly small molecular forms of CCK circulate in rabbits, and that NH2-terminal and mid-sequences of porcine and human CCK-33 differ from those of rabbit CCK-33. The results support the contention that plasma in most mammals contains small molecular forms of CCK.

Amino Acid Sequence↗
PubMed1994

The effect of gastrin-releasing peptide on porcine pancreaticobiliary bicarbonate secretion is mediated by secretin.

The effect of gastrin-releasing peptide (GRP) (250, 500, 1000 pmol/kg.h) on the pancreaticobiliary bicarbonate secretion, the pancreatic protein secretion, and the plasma concentrations of secretin and cholecystokinin (CCK) was studied in the anaesthetized pig. Infusion of GRP (1000 pmol/kg.h) increased the portal plasma concentrations of secretin from 0.9 to 13.6 pmol/l and CCK from 1.2 to 38.4 pmol/l, the pancreatic bicarbonate secretion from 0.01 to 5.6 mmol/h, the hepatic bicarbonate secretion from 0.5 to 4.1 mmol/h, and the pancreatic protein secretion from 3 to 680 mg/h. Blocking of CCK-A receptors by MK-329 did not significantly change the effect of GRP, whereas prevention of secretin release by removal of the small intestine caused a 13-fold reduction in the GRP-induced pancreatic bicarbonate secretion and completely abolished the effect on hepatic bicarbonate secretion but did not change the effect on pancreatic protein secretion. We conclude that the effect of GRP on pancreaticobiliary bicarbonate secretion is not mediated through the release of CCK but more likely through the release of secretin and that the effect on pancreatic protein secretion is possibly a direct effect of GRP.

Animals↗
PubMed1994

Effect of cionin on histamine and acid secretion by the perfused rat stomach.

BACKGROUND: The protochordean octapeptide cionin is structurally a hybrid of mammalian cholecystokinin (CCK) and gastrin. An earlier study has shown that cionin in mammals stimulates gallbladder contraction and gastric somatostatin release, similarly to CCK-8. METHODS: In the present study we examined the effect of cionin on histamine release and acid secretion of the stomach, both effects being mediated by CCK-B/gastrin receptors. RESULTS: Cionin induced a concentration-dependent increase in histamine release and acid secretion in the isolated, vascularly perfused rat stomach, detectable at a concentration of 4 pM and reaching a maximum at a concentration of 512 pM. The CCK-B/gastrin receptor antagonist L 365,260 abolished the stimulating effect of cionin on both histamine release and acid secretion, whereas the CCK-A receptor antagonist L 364,718 only had a faint effect. CONCLUSION: Cionin is a potent and efficient stimulator of gastric histamine release and acid secretion interacting via a CCK-B receptor.

Amino Acid Sequence↗
PubMed1994

Endogenous gastrin and cholecystokinin do not promote growth of rat liver.

BACKGROUND: The purpose of the study was to evaluate the trophic effects of endogenous hypergastrinemia and hypercholecystokininemia on intact and regenerating rat liver. We also examined the effects on the liver of portacaval shunting (PCS) alone or together with hypergastrinemia or hyperCCKemia. PCS is known to enhance the trophic effects of gastrin on the so-called enterochromaffin-like cells of the stomach and of CCK on the pancreas. METHODS: Hypergastrinemia was induced by treatment with omeprazole (400 mumol/kg/day) or extirpation of the acid-producing part of the stomach (fundectomy). HyperCCKemia was induced by pancreaticobiliary diversion (PBD). After 4 weeks half of the rats were killed; the rest underwent partial hepatectomy and were killed 60 h later. PCS rats were killed 4 weeks after start of omeprazole treatment or after PBD. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The liver weight and DNA content were analyzed. RESULTS: Endogenous hypergastrinemia and hyperCCKemia failed to stimulate growth of either intact or regenerating liver. There were no differences in liver weight and DNA content between rats subjected to PCS and to combinations of PCS and omeprazole treatment, on the one hand, and PCS and PBD, on the other. CONCLUSION: Gastrin and CCK are unlikely to be physiologically important in the regulation of liver growth and regeneration in the rat.

Animals↗
PubMed1994

Endogenous hypercholecystokininemia, but not aspirin, reduces the gallstone incidence in the hamster model.

BACKGROUND: Studies in humans and rodents indicate that gallstone development may be prevented by inhibiting gallbladder mucus hypersecretion with non-steroidal anti-inflammatory drugs or by preventing stasis of gallbladder bile with administration of cholecystokinin. METHODS: The effect of oral aspirin and pancreaticobiliary diversion with endogenous hypercholecystokininemia on crystal and gallstone formation was studied in Syrian golden hamsters fed a lithogenic diet for 8 weeks. RESULTS: None of the control animals fed a normal diet developed gallstones or crystals in gallbladder bile. Gallstones developed in 67% of the animals fed a lithogenic diet only. The gallstone prevalence did not differ significantly in animals on a lithogenic diet and a daily aspirin dose of 6 mg/kg (gallstone prevalence, 60%) or 100 mg/kg (gallstone prevalence, 70%), whereas it was significantly lower in animals with endogenous hypercholecystokininemia on a lithogenic diet (gallstone prevalence, 29%). The prevalence of crystals in gallbladder bile did not differ significantly between any of the experimental groups. CONCLUSIONS: It is concluded that in hamsters on a lithogenic diet, aspirin does not prevent gallstone formation, whereas endogenous hypercholecystokininemia reduces the prevalence of stones without affecting the occurrence of crystals in gallbladder bile.

Animals↗
PubMed1994

Effects of gastric fundusectomy and antrectomy on gallbladder epithelial proliferation in the hamster.

BACKGROUND: Exogenous administration of cholecystokinin or its analog cerulein induces epithelial hyperplasia in the mouse gallbladder. The effects on the gallbladder of resectional surgery of the stomach with hormonal consequences are not known. METHODS: The effects of gastric fundusectomy and antrectomy on proliferation and growth of the gallbladder epithelium were studied in male Syrian golden hamsters during periods of 5 and 25 days. Sham-operated animals served as controls. RESULTS: Basal plasma gastrin concentrations were significantly increased after fundusectomy and significantly decreased after antrectomy, whereas basal plasma cholecystokinin concentrations were not significantly affected. Five days after fundusectomy, there was a significant increase in the tritiated thymidine DNA labeling index of gallbladder epithelial cells. On day 25, the gallbladder weight and total number of epithelial cells were significantly increased after fundusectomy. Antrectomy significantly decreased the gallbladder weight on day 25, whereas the labeling index and total number of epithelial cells were not significantly affected on days 5 and 25. CONCLUSIONS: These results suggest that gastric fundusectomy at least transiently induces gallbladder epithelial hyperplasia and hypertrophy in the hamster. Although achlorhydria and hypergastrinemia are prominent features, the actual mechanism behind this effect of fundusectomy on the gallbladder needs further clarification.

Animals↗
PubMed1993

cDNA deduced procionin. Structure and expression in protochordates resemble that of procholecystokinin in mammals.

Using an improved 3' RACE (PCR) amplification system containing oligonucleotide primer with an inosine at ambiguous codon positions and inverse PCR to amplify the 5' ends, we have isolated and characterized cDNA clones which encode cionin, a protochordean homologue of the mammalian hormones, cholecystokinin (CCK) and gastrin. The full-length cloned cDNA of 510 bp encoded a 128 amino acid preprocionin. Reverse transcription-PCR and subsequent cDNA cloning revealed that cionin mRNA is expressed in both the neuronal ganglion and the gut of the protochordate Ciona intestinalis. The primary structure of procionin resembles that of proCCK more than that of progastrin. Sequence-specific immunochemical analysis showed that the cionin gene is expressed also at peptide level in both the gut and the neural ganglion. The neuronal processing of procionin is, however, more complete both with respect to carboxyamidation and tyrosine O-sulfation. Hence, the tissue-specific expression of the cionin gene in Ciona intestinalis resembles that of the CCK gene in mammals.

Amino Acid Sequence↗
PubMed1993

N-terminal fragments of intestinal cholecystokinin: evidence for release of CCK-8 by cleavage on the carboxyl side of Arg74 of proCCK.

From porcine duodenal mucosa we have identified three major procholecystokinin (proCCK) fragments: desoctaCCK-33, desnonaCCK-33 and desnonaCCK-39. (DesoctaCCK-33 means CCK-33 devoid of the 8 C-terminal amino acids, etc.). The fragments were purified by immunoaffinity chromatography and three steps of reverse phase HPLC monitored by a radioimmunoassay specific for the N-terminal part of CCK-33. The structures could be deduced from the proCCK sequence by N-terminal sequence determination and mass spectrometry. Whereas desnona-fragments of CCK have been described before, this is the first finding of a desoctaCCK, and it indicates that CCK-8 is released from the longer forms by endogenous cleavage of the Arg-Asp-bond. A carboxypeptidase B-like exopeptidase subsequently must produce the desnona-fragments by removing the arginine residue.

Amino Acid Sequence↗
PubMed1993

LymnaDFamides, a new family of neuropeptides from the pond snail, Lymnaea stagnalis. Clue to cholecystokinin immunoreactivity in invertebrates?

Five tridecapeptides have been identified from the central nervous system of the pond snail, Lymnaea stagnalis. The sequences are Pro-Xaa-Asp-Arg-Ile-Ser-Yaa-Ser-Ala-Phe-Ser-Asp-Phe. NH2, where Xaa is either Tyr or Phe and Yaa either Asn, Ser or Gly. The peptides are named lymnaDFamides to acknowledge identity with the C-terminal dipeptide of the mammalian neuropeptides, cholecystokinin (CCK) and gastrin. They were detected by an antiserum that recognizes the biologically active C-termini of cholecystokinin and gastrin. LymnaDFamide-1 (Xaa = Tyr and Yaa = Asn) had no effect on trout gallbladder, which responds equally to CCK and gastrin. We propose that the lymnaDFamides belong to an Asp-Phe-amide superfamily, which includes CCK and gastrin, and suggest that the widespread CCK/gastrin immunoreactivity in invertebrates is due to peptides belonging to such a superfamily.

Amino Acid Sequence↗
PubMed1993

Ovarian cancers express and process progastrin.

Gastrin synthesis in ovarian tumors has been described in a few isolated cases associated with the Zollinger-Ellison syndrome. Consequently, ovarian gastrin synthesis has been considered exceptional. In order to evaluate whether expression of gastrin in ovarian tumors indeed is rare, we examined the expression and processing of progastrin in 16 malignant and 5 benign ovarian tumors and 4 normal postmenopausal ovaria. Using a library of sequence specific radioimmunoassays, cleavage by processing-like enzymes, and gel chromatography, we found that one-half of the malignant tumors expressed significant concentrations of amidated gastrins [6.7 +/- 2.7 (SEM) pmol/g; range, 1.4-20.0 pmol/g, n = 7]. The concentrations of glycine-extended gastrins and progastrins were low (0.25 +/- 0.03 and 1.4 +/- 0.4 pmol/g, respectively) but higher than in controls and benign tumors. Chromatography showed that the majority of the bioactive gastrins was unsulfated gastrin-17. The other half of the malignant tumors expressed glycine-extended gastrins and progastrins (0.2 +/- 0.03 and 0.6 +/- 0.1 pmol/g; n = 9), but the amidation of the peptides was impaired (0.1 +/- 0.03 pmol/g). Low concentrations of glycine-extended gastrins and progastrins were detected in the normal ovarian tissues (0.2 +/- 0.05 pmol/g tissue and 0.2 +/- 0.06 pmol/g, respectively, n = 4) and in the benign tumors (0.1 +/- 0.02 pmol/g and 0.5 +/- 0.03 pmol/g; n = 5). Amidated gastrins were undetectable, except in low amounts in a single benign tumor (0.2 pmol/g tissue). The results show that postmenopausal ovaria and neoplastic ovarian tissues express the gastrin gene at peptide level. The synthesis and processing of progastrin increase considerably in malignant tumors.

Cholecystokinin↗
PubMed1993

Colonic mucosal proliferation after pancreaticobiliary diversion in the hamster.

The effect of pancreaticobiliary diversion (PBD) on the colonic mucosa was studied in hamsters over 5, 10, and 24 days. Sham-operated animals served as controls. At all three time intervals, experimental animals had increased plasma cholecystokinin concentrations and decreased gastrin concentrations. Five days after PBD, there was an increase in scintigraphically measured [3H]thymidine incorporation into colonic tissue. Correspondingly, there was an increase in the [3H]thymidine DNA labeling index of goblet cells in the colonic mucosa. The total number of cells in the colonic crypt columns were significantly increased on days 5, 10 and 24. Whether this proliferative response in the colon is due to increased release of cholecystokinin, enteroglucagon, other aberrations of hormones or growth factors, or simply an increased bile load on the colonic mucosa remains to be clarified. Such further studies may reveal an alternative animal model for studies on risk factors in colonic carcinogenesis.

Animals↗
PubMed1993

Developmental expression of the gastrin and cholecystokinin genes in rat colon.

BACKGROUND: To elucidate the hypothesis that gastrin and cholecystokinin (CCK) are local growth factors for colorectal mucosa, we have examined the peptide gene expression in rat colon during development. METHODS: Northern analysis, reverse transcription PCR, and sequence-specific radioimmunoassays were the essential methods. RESULTS: High concentrations of gastrin and CCK messenger RNA were found in the fetal colon. At birth, gastrin and CCK mRNA's were both undetectable but increased subsequently towards adult life. The fetal colon contained 5.5 and 4.2 pmol/g tissue gastrin and CCK, respectively. After birth, carboxyamidated gastrin disappeared from the colon, whereas the concentration of CCK remained at 1 pmol/g. Glycine-extended gastrin and CCK were also present in the fetal colon, but towards adult life they decreased below 0.2 pmol/g. In contrast, progastrin and proCCK were detectable at all ages. CONCLUSIONS: Rat colon expresses the gastrin and CCK genes throughout life. The posttranslational maturation of progastrin, however, ceases shortly after birth, indicating that gastrin may play a role in the developing colon. Whether CCK influences the development remains to be shown.

Aging↗
PubMed1993

Expression but incomplete maturation of progastrin in colorectal carcinomas.

BACKGROUND: To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue. METHODS: Northern analysis, reverse-transcription PCR, and a library of sequence-specific radioimmunoassays were the principal methods. RESULTS: Cell lines, tumors, and normal tissue all expressed a gastrin mRNA of 0.7 kilobases, and all cell lines contained incompletely processed progastrin (range, 17-54 fmol/10(6) cells). Two cell lines secreted progastrin into the media (LoVo, 25 +/- 3 pmol/L; HCT116; 12 +/- 2 pmol/L). Normal colonic tissue and all the solid tumors also contained progastrin, the concentration being higher in tumors (range, 0.4-2 pmol/g) than in normal tissue (range, 0.1-0.2 pmol/g). Only one tumor contained carboxyamidated gastrins. CONCLUSIONS: Normal and neoplastic colonic mucosa both express the gastrin gene, but the posttranslational phase of expression is attenuated. The incomplete processing and low level of expression suggest that autocrine gastrin secretion has only minor significance for normal adult and most neoplastic colonic tissue.

Actins↗