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Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 109 records · Page 6Linked to original sources
PubMed1994

Acetylcholine regulates glucagon secretion from human glucagonoma cells.

Human glucagonoma cells were isolated and maintained in vitro. Incubation experiments showed that carbachol (Cch) induced the simultaneous release of glucagon, VIP (vasoactive intestinal polypeptide), and pancreatic polypeptide (PP) at levels significantly higher than basal levels. Atropine abolished the stimulatory effect of Cch on glucagon, VIP, and PP release. An immunohistological study of the tumor tissues revealed that the cells contained glucagon, VIP, and PP. These findings demonstrate, for the first time, the in vitro release of glucagon from glucagonoma cells by Cch stimulation.

Carbachol↗
PubMed1994

Effect of a new cholecystokinin antagonist (FK 480) on gene expression of cholecystokinin and secretin in rat intestine.

The effects of a new cholecystokinin (CCK) antagonist (FK 480; 0.1 mg/kg per day given by intragastric administration to rats for 3 days) on the expression of the CCK and secretin genes, plasma CCK immunoreactivity, and CCK content in the intestinal mucosa were examined. FK 480 increased the level of CCK mRNA in the intestine to 1.7 times the level in control rats, but did not affect the level of secretin mRNA. It did not increase plasma CCK immunoreactivity or CCK content in the intestinal mucosa. These results suggest that the ingested FK 480 directly increased CCK mRNA level in the intestine and produced a dissociation between the synthesis and release of CCK.

Animals↗
PubMed1994

Expression of the cholecystokinin precursor gene in rat tissues.

Cholecystokinin, a brain gut peptide that stimulates gall bladder contraction and pancreatic exocrine secretion, also acts as a neurotransmitter. In this study, we demonstrated that small amounts of cholecystokinin precursor mRNA were expressed in the heart, lung, and kidney, as well as in the brain and the small intestine. The nucleotide sequences of the coding regions of the cholecystokinin precursor mRNA in these tissues were identical to those of the small intestine, indicating that cholecystokinin precursor proteins produced in these tissues are identical to those in small intestine. This is the first report demonstrating that the cholecystokinin precursor gene is expressed in the heart, lung, and kidney, as well as in the gastrointestinal tract and brain.

Animals↗
PubMed1994

Pancreastatin molecular forms in normal human plasma.

Circulating molecular forms with pancreastatin (PST)-like immunoreactivity in plasma from normal subjects were examined. An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] (hPST-52) and a larger form (mol wt 15-21 kDa) were detected by gel filtration of plasma from normal subjects. On high performance liquid chromatography, predominant immunoreactive forms coeluted with the three larger forms which were purified from the xenograft of human pancreatic islet cell carcinoma cell line QGP-1N cells and with synthetic hPST-52. The fraction containing larger forms purified from xenograft of QGP-1N cells had biological activity equivalent to that of hPST-52 on the inhibition of pancreatic exocrine secretion. These results suggest that the larger molecular forms as well as hPST-52 may be physiologically important circulating forms of PST in human.

Animals↗
PubMed1994

Glucagon-like peptide-1 (GLP-1) molecular forms in human pancreatic endocrine tumors resemble those in intestine rather than pancreas.

Different glucagon-like peptide-1 (GLP-1) molecular forms are produced in the pancreas and the small intestine by differential processing of proglucagon. In this report, molecular forms of GLP-1 in two human pancreatic endocrine tumors were studied and compared with those in the pancreas and small intestine. A predominant GLP-1 immunoreactive form in the pancreas was eluted at the position of GLP-1(1-36) amide, whereas a predominant immunoreactive form in the ileal mucosa was eluted at the position of GLP-1(7-36) amide. In a glucagonoma, GLP-1 immunoreactive forms corresponding to GLP-1(7-36) amide and GLP-1(7-37) were predominant and immunoreactive forms at the position of GLP-1(1-36) amide and GLP-1(1-37) were minor. In another tumor, an insulinoma, immunoreactive forms were detected at the positions of GLP-1(7-36) amide, GLP-1(7-37), GLP-1(1-36) amide and GLP-1(1-37). Thus, the pattern of GLP-1 molecules in pancreatic tumors was not a pancreatic pattern and mimicked that found in the small intestine or consisted of both the patterns found in the small intestine and the pancreas. These data suggest that neoplastic transformation of the islet cells is associated with a switching in processing phenotype from islet (A) cells to intestinal (L) cells.

Chromatography, High Pressure Liquid↗
PubMed1994

Mechanisms of stimulatory effect of neuromedin C on pancreatic exocrine secretion in conscious rats.

The mechanisms of the stimulatory effect of the bombesin-like peptide neuromedin C on pancreatic exocrine secretion were examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. Intravenous infusion of 0.35 nmol/kg/h of neuromedin C significantly increased the secretions of pancreatic bicarbonate and protein, and transiently increased the plasma cholecystokinin (CCK) concentration. The increase in pancreatic secretion persisted for 90 min, whereas the increase in plasma CCK was observed only after 15 and 30 min from the beginning of neuromedin C infusion. Intravenous infusion of CR-1409, a specific CCK-receptor antagonist, inhibited, but did not abolish, the protein secretion stimulated by neuromedin C. Intraduodenal infusion of a potent proton pump inhibitor, omeprazole, suppressed, but did not abolish, protein secretion induced by neuromedin C. Omeprazole abolished the increase in bicarbonate secretion produced by neuromedin C. These results indicate that neuromedin C induces release of CCK and that its induction of pancreatic hypersecretion is due to both its direct effect and CCK. The results also suggest that gastric hypersecretion may have a role in the bicarbonate hypersecretion induced by neuromedin C.

Animals↗
PubMed1994

Lack of effect of cholecystokinin receptor antagonist (CR1505) on recovery of experimental pancreatitis after pancreatic duct occlusion in rats.

The effect of long term administration of a synthetic cholecystokinin (CCK) receptor antagonist CR1505 (loxiglumide) on pancreatitis was examined in rats after pancreatic duct ligation (PL) with an internal bile fistula. All rats were given both 6 mg/day of CR1505 continuously infused intraduodenally with an osmotic pump and 32 mg/day introduced into the stomach with an orogastric tube. Rats were killed 7, 14, and 28 days after PL, and changes of body weight, pancreatic wet weight, daily food intake, pancreatic protein content, and histology, plasma amylase concentration, and both plasma and duodenal CCK concentrations were examined. Administration of CR1505 for 7 days from immediately after PL, resulted in decrease of body weight, increase of daily food intake, and significant increases of intestinal CCK concentration and the level of CCK mRNA. However, its administration from day 7 to day 14 or 28 did not improve any of the parameters examined except inflammatory infiltration of the pancreas on the 14th postoperative day. These results suggest that CR1505 may have a beneficial effect on recovery from pancreatitis when administered during the early stage, but not when administered during a later stage.

Animals↗
PubMed1994

Effectiveness of chemotherapy for advanced adenocarcinoma of the pancreas in combined modality therapy.

Because it is difficult to diagnose at an early stage, pancreatic carcinoma is usually well advanced by the time it is diagnosed. The combined use of intraoperative radiotherapy, gastrointestinal and/or biliary tract bypass operation, celiac plexus nerve block, and chemotherapy is widely applied in treatment, with favorable results reported in some patients with advanced disease. To evaluate the efficacy of chemotherapy in such combinations, we compared the effect of 5-fluorouracil, its analogues, and mitomycin C on the survival of patients with advanced stage pancreatic cancer. We found no significant difference between the patients treated or not treated with these drugs. Clearly, there is a need for new agents having greater efficacy against pancreatic carcinoma.

Adenocarcinoma↗
PubMed1994

Gene expression of erythropoietin in hepatocellular carcinoma.

A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.

Aged↗
PubMed1994

Secretory capacity of pancreatic protein during luminal feedback regulation in conscious rats.

Pancreatic exocrine secretion in conscious rats is regulated by bile and pancreatic juice in the proximal intestine (luminal feedback regulation), and bile-pancreatic juice diversion from the intestine results in cholecystokinin (CCK) release and pancreatic hypersecretion. Pancreatic protein secretion increases to a maximum 60-90 min after bile-pancreatic juice diversion, and then decreases slightly to a steady level of two times the basal level. Change in plasma CCK concentration parallels protein secretion. In this study, the mechanism of the decreases of protein secretion and CCK concentration was examined by stimulation with various species of peptides having different stimulatory mechanisms. Cannulae for draining bile and pancreatic juice separately and a duodenal cannula and extrajugular vein cannula were inserted into male Wistar rats. Four days later, basal levels in a 90-min period were determined, bile and pancreatic juice were diverted for 90 min, and then either secretin (1.2 nmol/kg/h), CCK-8 (25 and 100 pmol/kg/h), neuromedin C (350 pmol/kg/h and 3.5 nmol/kg/h), or CCK-JMV-180 (200 nmol/kg/h) was infused intravenously for 60 min. Infusion of secretin significantly increased protein secretion and prevented its decrease after its maximum induced by bile-pancreatic juice diversion. The plasma CCK concentrations were not increased further by neuromedin C. In conclusion, pancreatic exocrine secretion and CCK release in conscious rats are maximally stimulated by luminal feedback regulation that the decrease after maximal protein output may be due to limitation of secretory capacity and/or desensitization of acinar cells.

Animals↗
PubMed1994

Time course of recovery from pancreatic hypertrophy during partial exclusion of bile-pancreatic juice in rats.

The time course of recovery from hypertrophied pancreas to the normal size was examined and compared with the time course of normal size pancreas getting hypertrophied in rats. The bile-pancreatic duct was cannulated and bile-pancreatic juice was partly bypassed the proximal intestine. Trypsin and bile salts disappeared from the lumen of proximal quarter of intestine during the first 7 postoperative days; however, these appeared again after the 14th postoperative day and luminal trypsin activity reached 3 to 4 times the control level during the postoperative days 14-56. Conversely, the plasma cholecystokinin (CCK) concentration significantly increased on day 7, then declined thereafter, and the mRNA level of CCK in the proximal intestinal mucosa increased and reached the maximal level on day 7. Pancreatic wet weight, as an index of size, was significantly increased and remained high on postoperative days 7-28, then returned to the control size on day 56. Therefore, it took 7 d for the pancreas to become hypertrophied by high circulating CCK, however the pancreatic size recovered to the normal size on the 56th postoperative day although the plasma CCK level decreased with the appearance of luminal bile salt and trypsin during postoperative days 14-56. In conclusion, it took longer for the hypertrophied pancreas to return to the normal size (14 or more d) than for the normal size pancreas to become hypertrophied (7d).

Animals↗
PubMed1994

[Effect of bilateral truncal vagotomy on cholecystokinin release and pancreatic exocrine secretion in conscious rats].

The effects of bilateral truncal vagotomy on cholecystokinin (CCK) release and pancreatic hypersecretion produced by bile and pancreatic juice (BPJ) diversion were examined in conscious rats. In addition, the effect of exogenous administration of CCK-8 (100 pmol/kg/h) on pancreatic secretion were compared in rats with and without vagotomy. Rats were prepared with external bile and pancreatic juice fistulae and the experiment was conducted on the 4th postoperative day. Basal pancreatic secretion was not affected by vagotomy. CCK release produced by bile and pancreatic juice diversion was enhanced, whereas protein secretion in response to high plasma CCK was inhibited by vagotomy. Pancreatic secretion stimulated by intravenous infusion of 100 pmol/kg/h of CCK-8 was also inhibited by vagotomy. These results proposed that vagal nerve is mandatory for the full response of pancreatic exocrine secretion to circulating CCK.

Animals↗
PubMed1994

In vitro release of vasoactive intestinal polypeptide and pancreatic polypeptide from human VIPoma cells and its inhibition by somatostatin analogue (SMS 201-995).

BACKGROUND: The purpose of the present study was to determine whether vasoactive intestinal polypeptide (VIP) is released from the tumor cells of VIPoma and if so then to attempt to show how its release is regulated by cultured human VIPoma cells. METHODS: A resected specimen of a pancreatic tumor from a patient with watery diarrhea, hypokalemia, and achrohydria syndrome was examined. The dissociated cells were obtained by collagenase digestion of the tumor tissue and were cultured in vitro. RESULTS: The extraction of tumor cells disclosed that the cells contained VIP and pancreatic polypeptide (PP). Neither insulin, glucagon, somatostatin nor pancreastatin was detected. Immunohistochemically, 40% to 60% of the cells in the tumor stained positively for VIP and 1% to 5% stained positively for PP. The dissociated cells became reaggregated in the culture (50 to 300 microns) and could be maintained in vitro. Incubation experiments revealed a simultaneous in vitro release of VIP and PP with a significant increase by either carbachol or phorbol myristate acetate but not by theophylline or caerulein. Atropine completely abolished the stimulatory effects of carbachol on VIP and PP release. Octreotide (somatostatin analogue [SMS 201-995]) significantly inhibited the carbachol and phorbol myristate acetate-stimulated VIP and PP release. CONCLUSIONS: These findings show the in vitro release of VIP and PP from the VIPoma cells and also provide evidence for the direct inhibitory effect of somatostatin analogue on both the VIP and PP release from the tumor cells.

Adult↗
PubMed1993

Secretion of neurotensin from a human pancreatic islet cell carcinoma cell line (QGP-1N).

Effects of various secretagogues on secretion of neurotensin from a pancreatic islet cell carcinoma cell line (QGP-1N) were examined. Carbachol stimulated secretion of neurotensin concentration-dependently in the range of 10(-6) - 10(-4) M. The neurotensin secretion stimulated with 10(-5) M carbachol was completely inhibited by atropine at 10(-5) M. Phorbol ester and calcium ionophore (A23187) stimulated secretion of neurotensin. The removal of extracellular Ca2+ suppressed the secretion through the stimulation with 10(-5) M carbachol. Fluoride, an activator of guanine nucleotide-binding (G) protein, stimulated secretion of neurotensin. Neurotensin released into culture medium through stimulation with carbachol coeluted with neurotensin 1-13 on a gel-chromatography. Our results suggest that secretion of neurotensin from QGP-1N cells is mainly regulated by acetylcholine through muscarinic receptors coupled to G protein and that an increase in intracellular Ca2+ and protein kinase C play an important role in stimulus-secretion coupling.

Calcium↗
PubMed1993

Gene expression of mutant erythropoietin in hepatocellular carcinoma.

A case of hepatocellular carcinoma complicated by erythrocytosis showed an increased level of serum immunoreactive erythropoietin (EPO) and EPO bioactivity. RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. The nucleotide sequences of PCR amplified regions of the EPO precursor mRNA in tumor tissue showed three differences to those of normal EPO cDNA. The deduced amino acid sequence of the coding region also showed three differences from that of normal EPO. The erythrocytosis improved and the high serum EPO immunoreactive and bioactive level decreased after resection of the tumor. This is the first demonstration of mutant EPO mRNA expression and bioactive mutant EPO protein in hepatocellular carcinoma tissue.

Aged↗
PubMed1993

Cholinergic dependency of stimulatory effects of neurotensin on exocrine pancreas in rats.

The biological activities of neurotensin, a 13-residue peptide, on the exocrine pancreas were examined in vitro using dispersed pancreatic acini and in vivo using conscious rats. Neurotensin had weak amylase stimulatory activity in vitro, but its injection at 0.6 or 2 nmol/kg/h stimulated pancreatic exocrine secretion in vivo. CR-1409, a cholecystokinin (CCK) receptor antagonist, partially inhibited neurotensin-stimulated pancreatic secretion, although neurotensin did not stimulate plasma CCK release. Atropine completely inhibited the pancreatic response to neurotensin. These results suggest that neurotensin has either a direct biological action on the exocrine pancreas or an action mediated by cholinergic nerve transmission, and that neurotensin does not have a major physiological role in inducing pancreatic secretion.

Amylases↗