Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 181 records · Page 10Linked to original sources

PubMed1989

Effects of synthetic human gastrin-releasing peptide on pancreatic exocrine secretion and release of pancreatic polypeptide in conscious rats.

The effects of a newly synthesized peptide, human gastrin-releasing peptide (hGRP), on the pancreatic exocrine secretion and the release of pancreatic polypeptide (PP) were examined in the conscious rat. Plasma PP concentrations were determined by a recently established specific radioimmunoassay for rat PP. Amounts of 0.18, 0.35, and 3.5 nmol/kg/h hGRP significantly stimulated both pancreatic exocrine secretion and 0.35 nmol/kg/h of hGRP increased PP release. Simultaneously infused proglumide (300 mg/kg/h) did not affect either pancreatic exocrine secretion or PP release. However, simultaneous infusion of atropine (100 micrograms/kg/h) slightly inhibited PP release, but did not restrict the incremental response of pancreatic protein secretion to hGRP. These results suggest that hGRP directly stimulates pancreatic exocrine secretion and PP release.

Animals↗

PubMed1989

High plasma pancreastatinlike immunoreactivity in a patient with malignant insulinoma.

High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin A corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography.

Adenoma, Islet Cell↗

PubMed1989

Effect of secretin and caerulein on pancreatic polypeptide and on insulin secretion from the isolated perfused ventral area of the rat pancreas.

The secretion of pancreatic polypeptide (PP) and insulin (IRI), stimulated by secretin or caerulein was investigated in the isolated perfused ventral area of the rat pancreas. The effect of atropine on these secretory responses was examined. Secretin (100-1000 pM) stimulated transient PP secretion and this response was completely inhibited by 10 microM of atropine. However, 10 pM secretin and 10-1000 pM caerulein did not stimulate the secretion of PP. Caerulein transiently stimulated IRI secretion and this response was not inhibited by atropine, but 10-1000 pM secretin did not stimulate IRI secretion. Therefore, the supraphysiological dose of secretin stimulates PP secretion probably via an intrapancreatic release of acetylcholine, while caerulein stimulates IRI secretion by a direct action.

Animals↗

PubMed1989

Effect of pancreastatin on pancreatic endocrine function in the conscious rat.

We have studied the effects of pancreastatin on insulin and glucagon secretions in vivo in the conscious rat. Rats were prepared with a gastric fistula and with both external jugular veins cannulated. We found that an i.v. infusion of pancreastatin (1 and 10 nmol/kg/h) inhibited the plasma insulin response and increased the plasma glucose response to the intragastric infusion of glucose in a dose-dependent manner. Furthermore, the infusion of pancreastatin increased the plasma glucagon response to the i.v. infusion of arginine in a dose-dependent manner, and it inhibited the plasma insulin response. However, such an infusion of pancreastatin had no effect on the basal plasma glucose level, nor did it have any effect on plasma insulin and glucagon concentrations. Thus, it is suggested that in the rat, the newly discovered pancreastatin is a regulator of islet cell function.

Animals↗

PubMed1989

Inhibitory effect of pancreastatin on pancreatic exocrine secretion in the conscious rat.

The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.

Amylases↗

PubMed1989

Isolation and characterization of bovine pancreastatin.

Bovine pancreastatin, a 47 amino acid residue peptide, was isolated from the pancreas and the pituitary gland using a chemical method which detects its C-terminal glycine amide structure. The complete amino acid sequence of the pancreatic peptide is 74% homologous to that of porcine pancreastatin and is identical to bovine chromogranin A-(248-294), as deduced from its cDNA sequence. The sequence of the first 28 amino-terminal residues of the pituitary peptide was determined to be identical to the corresponding sequence of the pancreatic peptide. Since the pituitary peptide also contains the C-terminal glycine amide, it is therefore likely to be identical in structure to the pancreatic peptide. Thus, we conclude that bovine chromogranin A is the precursor of bovine pancreastatin. Synthetic bovine pancreastatin inhibited pancreatic exocrine secretion in a similar manner to porcine pancreastatin.

Animals↗

PubMed1989

Plasma cholecystokinin and pancreatic polypeptide responses after ingestion of a liquid test meal rich in medium-chain fatty acids in patients with chronic pancreatitis.

Plasma cholecystokinin (CCK) and human pancreatic polypeptide (hPP) responses after ingestion of a liquid test meal rich in medium-chain fatty acids (MCFA) were studied in patients with chronic pancreatitis with or without diabetes mellitus (DM). Integrated response of plasma CCK was significantly lower in patients with chronic pancreatitis and DM than in the two other groups. There was no statistically significant difference between the healthy control subjects and the patients with chronic pancreatitis without DM in the integrated responses of hPP and plasma CCK. These results indicate that diabetic patients with a greatly destroyed pancreas do not release as much CCK as do nondiabetic patients with a mildly impaired pancreas. An MCFA meal is therefore considered safe in patients with a mildly impaired pancreas. For diabetic patients, however, care should be taken not to exacerbate the DM.

Adult↗

PubMed1989

Stimulatory effect of monitor peptide and human pancreatic secretory trypsin inhibitor on pancreatic secretion and cholecystokinin release in conscious rats.

The stimulatory effects of monitor peptide (MP) that was recently purified from rat bile-pancreatic juice on cholecystokinin (CCK) release and pancreatic exocrine secretions were examined in the conscious rat. As the sequence of MP has some homology with human pancreatic secretory trypsin inhibitor (hPSTI), the effects of these two materials were compared with each other. Rats were prepared with external bile and pancreatic fistulae. Pancreatic juice diversion significantly increased pancreatic secretions, but the intraduodenal injection of MP (0.9 micrograms per rat) could further increase pancreatic secretions. The MP injection produced significantly higher plasma CCK concentrations than the injection of isotonic saline solution did. Trasylol was infused simultaneously with pancreatic juice diversion to completely eliminate residual luminal protease activities. The MP (0.9 micrograms per rat) still showed the stimulatory effect, but hPSTI did not show any stimulatory effect on pancreatic secretion. Plasma CCK concentrations produced by MP were significantly higher than those produced by hPSTI. It was concluded that MP has a strong species specificity and that MP could stimulate CCK release and pancreatic exocrine secretions, not only via inhibiting luminal protease activities but also probably with a direct effect.

Animals↗

PubMed1989

Release of pancreatic polypeptide and its mechanism in luminal feedback regulation in the conscious rat.

Exclusion of bile and pancreatic juice (BPJ) from the proximal intestine increases the release of pancreatic polypeptide (PP) from 4.4 to 14.3 pM and its increase was diminished by the intravenous infusion of atropine (100 micrograms/kg/h) in conscious rats. Neither intravenous bolus injection nor continuous infusion of cerulein did increase plasma PP concentration. It is suggested that the increase in plasma PP concentration produced by BPJ diversion is regulated by cholinergic mechanism, but not by cholecystokinin (CCK) released despite the known fact that BPJ diversion increases plasma CCK concentration.

Animals↗

PubMed1989

Effects of porcine pancreastatin on postprandial pancreatic exocrine secretion and endocrine functions in the conscious rat.

The inhibitory effect of a newly discovered polypeptide, pancreastatin, on postprandial pancreatic exocrine secretions and endocrine functions was examined in the conscious rat with a chronic external bile, pancreatic and gastric fistula. The infusion of 100 and 200 pmol/kg/h of pancreastatin significantly inhibited meal-stimulated pancreatic secretion of fluid and protein but not bicarbonate in a dose-dependent manner. The infusion of 100 and 200 pmol/kg/h of pancreastatin increased plasma pancreastatin concentrations (mean +/- SE) up to 133.5 +/- 15.9 and 209.8 +/- 14.5 pM, respectively. However, the same doses of pancreastatin failed to inhibit postprandial insulin and gastrin releases and did not affect blood glucose levels. It is suggested that pancreastatin may be an inhibitor of postprandial pancreatic exocrine secretion. However, the doses used in the present study may not have been high enough to affect endocrine functions.

Animals↗

PubMed1989

Plasma pancreastatin-like immunoreactivity in various diseases.

Plasma pancreastatin (PST)-like immunoreactivity in normal subjects and patients with various diseases was estimated by a RIA, using antiserum raised against a synthetic C-terminal peptide of human PST deduced from the sequence of human chromogranin-A. The mean level +/- SEM was 13.2 +/- 0.6 pmol/L in normal subjects, but was significantly higher in patients with chronic renal failure (526.7 +/- 48.5). An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] and a larger form were detected by gel filtration of plasma from these patients, suggesting accumulation of the larger molecular form in these patients. A significant increase in PST-like immunoreactivity was also found in patients with liver cirrhosis (20.8 +/- 3.0 pmol/L), but not in patients with noninsulin-dependent diabetes mellitus, chronic pancreatitis, or pancreatic cancer. Elevated levels were found in 16 of the 21 patients with small cell lung carcinoma examined. High levels were also found in 3 of 11 patients with islet cell tumor.

Adenoma, Islet Cell↗

PubMed1989

A case of multiple endocrine neoplasia (MEN) type 1; the immunohistochemical and ultrastructural studies of its tumors and the analysis of hormones in tumor extracts.

We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).

Adenoma↗

PubMed1989

Vasoactive intestinal polypeptide stimulates cholecystokinin secretion in perfused rat duodenum.

We examined the effect of vasoactive intestinal polypeptide (VIP) on cholecystokinin (CCK) secretion from the isolated perfused rat duodenum. VIP stimulated CCK secretion mono-phasically in a concentration-dependent manner in concentrations ranging from 10(-9) to 10(-7) M, and 10(-7) M of VIP led to an increment of 82 +/- 25.8 fmole/3 min. The stimulatory effect of VIP on CCK was not inhibited by 10(-5) M atropine. These results suggest that VIP may directly stimulate CCK secretion from the duodenum and work as a non-cholinergic, peptidergic neurotransmitter.

Animals↗

PubMed1989

The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

The inhibitory effects of CR-1409, a new glutaramic acid derivative developed as a cholecystokinin (CCK) receptor antagonist, on caerulein-stimulated amylase secretion and on intracellular Ca2+ ([Ca2+]i) mobilization were studied in isolated rat pancreatic acini. Pancreatic acini were prepared by collagenase digestion method and loaded with 1 microM fura-2/AM for measurement of the intracellular free Ca2+ concentration. Amylase release was examined by a perifusion method. Stimulation with 10(-10) M caerulein, 10(-5) M carbachol, or 10(-8) M gastrin-releasing peptide (GRP) led to biphasic amylase release and increase in [Ca2+]i. CR-1409 at 1 and 5 microM inhibited, by 50 and 84%, respectively, the amylase secretion and increase in [Ca2+]i induced by 10(-10) M caerulein, and 25 microM CR-1409 completely inhibited both amylase secretion and increase in [Ca2+]i induced by caerulein. However, 25 microM CR-1409 did not inhibit unstimulated secretion of amylase or the secretions induced by carbachol and GRP, which are also mediated by changes in intracellular Ca2+. We conclude that CR-1409 acts as a specific inhibitor of the CCK receptor in the pancreas, and is useful in studies on the involvement of the release and action of CCK in vitro.

Amylases↗

PubMed1989

Differences in stimulatory effects between rat pancreatic secretory trypsin inhibitor-61 and -56 on rat pancreas.

Two types of pancreatic secretory trypsin inhibitors (PSTIs) were recently purified from rat pancreatic juice. One consisted of 61 (PSTI-61) and the other of 56 (PSTI-56) amino acid residues. PSTI-61 has been reported to elicit cholecystokinin (CCK) release when injected into the duodenum. Since no information has been available about the action of PSTI-56 on CCK release, the two PSTIs were compared for their stimulatory effect on CCK release and pancreatic exocrine secretions in conscious rats after intraduodenal administration. Rats were prepared with bile and pancreatic fistulae and with two duodenal cannulae. Pancreatic juice was excluded from the duodenum for 48 h prior to the experiment because rat PSTIs were trypsin sensitive. PSTI-61 significantly stimulated pancreatic secretions and increased plasma CCK concentrations from 3.6 to 6.5 pM, whereas PSTI-56 had no effect on either CCK release or pancreatic secretions. It is suggested that the action as a regulator for CCK release and pancreatic secretions is possessed only by PSTI-61, but not by PSTI-56.

Amino Acid Sequence↗

PubMed1989

Comparative effects of mammalian pancreastatins on the pancreatic exocrine secretion.

We have reported that porcine pancreastatin inhibits cholecystokinin (CCK)-stimulated pancreatic exocrine secretion in conscious rats. In the present study, the effects of mammalian pancreastatins on exocrine pancreatic functions in rats were compared using synthetic pancreastatins (porcine, bovine, human, and rat). Rats were prepared with cannulae draining pure pancreatic juice and bile separately and a duodenal cannula to return bile-pancreatic juice to the intestine and with a jugular vein cannula. After 90-min basal collection of pancreatic juice, CCK-8 (100 pmol/(kg.h] was infused for 3 h with or without pancreastatins (100 pmol/(kg.h]. All pancreastatins significantly inhibited protein output at an equivalent molar potency. These results suggest that mammalian pancreastatins have the same biological activity of a comparable magnitude and exert a similar biological action on the exocrine pancreas.

Amino Acid Sequence↗

PubMed1989

Interactions between bile and pancreatic juice diversions on cholecystokinin release and pancreas in conscious rats.

Pancreatic exocrine secretion in the conscious rat is regulated by proteases secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in its mechanism. It has also been reported that the absence of either pancreatic juice or bile in the duodenum could stimulate pancreatic secretion. Therefore, differences in CCK release responding to the exclusion of bile, pancreatic juice (PJ), or both bile and pancreatic juice (BPJ) from the intestine were examined by using a bioassay for cholecystokinin. Plasma CCK levels were increased by all three treatments compared with the basal value, the order of their effects being BPJ greater than PJ greater than bile diversion, and CCK concentrations produced by BPJ diversion were much greater than can be explained as simply summed effect of exclusions of bile and PJ. Pancreatic exocrine secretions were significantly increased by PJ and BPJ diversions, but the effect of bile diversion on the pancreas was not statistically significant. An additional infusion of CR-1409 (0.1 mg/rat), one of CCK receptor antagonists, inhibited exocrine function stimulated by BPJ diversion. We conclude (i) BPJ diversion is the strongest endogenous stimulant on CCK release; (ii) the potentiation between bile and PJ diversions is induced on CCK release; (iii) pancreatic protein secretion during BPJ diversion is mainly modulated by CCK.

Animals↗

PubMed1989

[Effect of pancreastatin on pancreatic exocrine secretion in vivo and in vitro].

The effects of pancreastatin on pancreatic exocrine secretion were examined both in vivo and in vitro in rats. Pancreastatin inhibited pancreatic fluid and protein outputs stimulated by the exclusion of pancreatic juice from the intestine with the intraduodenal infusion of Trasylol but did not inhibit bicarbonate output stimulated by HCl in vivo in conscious rats. However, pancreastatin did not affect amylase release from dispersed acini or Ca concentration in acinar cells. Therefore, it is concluded that pancreastatin inhibits pancreatic exocrine secretion but the effect is indirect.

Amylases↗