Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used the ELISA to measure the concentration of amyloid protein precursor with Kunitz type trypsin inhibitor domains (APPI) in CSF of dementia of the Alzheimer type (DAT) and examined the correlation of APPI with acetylcholinesterase (AChE) and somatostatin (SRIF). We found the APPI concentration in CSF of DAT to be significantly elevated compared with that of multi-infarct dementia and controls. We could significantly correlate APPI with AChE, but not correlate APPI with SRIF. The present results suggest that measurement of CSF APPI levels may be useful for diagnosis of DAT and the change of APPI may closely be associated with abnormality of acetylcholine system in DAT that has been reported.
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PMID:Amyloid beta protein precursors with kunitz-type inhibitor domains and acetylcholinesterase in cerebrospinal fluid from patients with dementia of the Alzheimer type. 137 55

A phosphoryl protein tyrosine phosphatase (PTPase) activity has been characterized in rat pancreatic acinar membranes using 32P-labeled poly(Glu,Tyr) as substrate. Acinar membranes exhibited a high affinity for the substrate, with an apparent Km of 0.46 microM and an apparent Vmax of 0.9 nmol.mg protein-1.min-1. Acinar membrane PTPase activity displayed specific characteristics of other PTPases; it was inhibited by the inhibitors Zn2+, orthovanadate and by the divalent cations Mn2+ and Mg2+, and was stimulated by the reducing-agent dithiothreitol. It was also inhibited by soybean trypsin inhibitor and stimulated by trypsin. Gel permeation of pancreatic acinar membranes gave a single peak of enzyme activity with an apparent molecular mass of 70 000 Da. Further purification by HPLC on DEAE revealed two peaks of PTPase activity at 120 mM and 180 mM NaCl. These two peaks reacted in a Western-blot procedure with anti-(peptide) serum directed towards conserved domain of PTPase as a common 67-kDa form associated with lower-molecular-mass proteolytic fragments (31-56 kDa). Incubation of pancreatic acini with somatostatin analogues, SMS 201-995 or BIM 23014, resulted in a stimulation of membrane PTPase activity. The stimulation was rapid and transient, with a maximal level reached within 15 min of addition. The two analogs stimulated PTPase activity in a dose-dependent manner with half-maximal activation occurring at 7 pM and 37 pM and maximal activation at 0.1 nM and 0.1-1 nM for SMS 201-995 and BIM 23014, respectively. The stimulated-membrane PTPase activity also eluted at an apparent molecular mass of 70 kDa in gel-permeation chromatography. The two analogs inhibited the binding of [125I-Tyr3]SMS 201-995 to pancreatic acinar membranes with similar relative potencies to that observed on stimulation of PTPase activity. We conclude that pancreatic acinar membranes possess a low-molecular-mass PTPase which is stimulated by somatostatin analogs at concentrations involving activation of membrane somatostatin receptors.
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PMID:Stimulation of a membrane tyrosine phosphatase activity by somatostatin analogues in rat pancreatic acinar cells. 149 47

The neuropeptide bombesin has been shown to stimulate secretion of several gastrointestinal hormones, including cholecystokinin (CCK). We have previously demonstrated that stimulation of CCK release by feeding is associated with an increase in steady-state intestinal CCK mRNA levels. The purpose of the present study was to determine whether bombesin stimulates CCK release in rats and, if so, to determine whether bombesin regulates CCK mRNA levels in a manner similar to that of feeding. To establish a proper dose of bombesin for stimulating CCK release, rats received 1-h intravenous infusions of 0.25, 1, 4, or 16 micrograms.kg-1.h-1 bombesin. Basal plasma CCK levels averaged 1.8 +/- 0.4 pM and increased to peak levels of 2.9 +/- 0.6 pM within 15 min of infusion with 4 micrograms.kg-1.h-1 bombesin (the maximally effective dose). With the use of this dose, rats then received infusions of bombesin or saline lasting up to 24 h. At 1, 2, 4, and 24 h, animals were killed for collection of plasma for CCK measurements and of intestine for measurements of intestinal CCK and somatostatin mRNA levels. Bombesin treatment stimulated an increase in plasma CCK levels at 1 h, but levels declined to basal by 4 h, where they remained at 24 h. Despite increasing plasma CCK levels, bombesin infusion, unlike dietary stimulation, had no effect on duodenal CCK mRNA levels. Finally, to determine whether the decrease in plasma CCK levels after prolonged bombesin treatment was due to tachyphylaxis, rats treated with bombesin for 4 h were also fed soybean trypsin inhibitor (a known stimulus of CCK secretion).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of intestinal cholecystokinin and somatostatin mRNA by bombesin in rats. 167 36

The gastrointestinal peptides, cholecystokinin (CCK) and somatostatin, are produced by discrete endocrine cells in the mucosa of the small intestine. Although somatostatin may inhibit CCK secretion, the mechanism by which this occurs is unknown. The present study was designed to determine the effect of somatostatin on intestinal CCK and somatostatin mRNA levels. Rats, prepared with indwelling intraduodenal and jugular cannulas, were first fed an elemental diet that did not stimulate CCK release. Next, as a means of stimulating CCK secretion, soybean trypsin inhibitor was added to the diet and perfused intraduodenally at 50 mg/h for 24 h. Trypsin inhibitor caused an 11-fold increase in plasma CCK levels and a 2.4-fold increase in duodenal CCK mRNA levels. Simultaneous intravenous infusion of somatostatin-14 (1-100 micrograms.kg-1.h-1) reduced trypsin inhibitor-stimulated CCK levels by 50% and lowered trypsin inhibitor-stimulated CCK mRNA levels by 58%. Somatostatin infusion also reduced intestinal somatostatin mRNA levels stimulated by trypsin inhibitor but did not affect basal somatostatin mRNA levels. Duodenal CCK and somatostatin peptide concentrations did not change under any of the experimental conditions. These studies demonstrate that somatostatin reduces duodenal CCK mRNA levels stimulated by diet and suggest that somatostatin itself inhibits duodenal somatostatin gene expression.
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PMID:Somatostatin regulates duodenal cholecystokinin and somatostatin messenger RNA. 196 32

Regulation of endocrine pancreatic hormone gene expression by cholecystokinin (CCK) was examined in the rat using cloned cDNA probes to quantify changes in specific mRNAs (insulin, glucagon, pancreatic polypeptide and somatostatin). Plasma CCK levels were raised to concentrations comparable to physiologic postprandial values either by including soybean trypsin inhibitor (SBTI) in the intraduodenal perfusate of an elemental diet (6.9 +/- 1.0 pM, n = 6), or by intravenous infusion of CCK-8 (6.0 +/- 0.9 pM, n = 6). SBTI infusion for 48 h resulted in a three- to fourfold increase in procarboxypeptidase B and kallikrein mRNA levels. Similar increases were observed when CCK was infused intravenously for 24 h. In contrast, neither SBTI intraduodenally, nor intravenous CCK had any effects on mRNA levels of insulin, glucagon, PP or somatostatin. These data therefore indicate that CCK at physiologic postprandial plasma concentrations stimulates pancreatic protease gene expression but has no effects on gene expression of endocrine pancreatic hormones.
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PMID:Effects of CCK on gene expression of endocrine pancreatic hormones. 226 71

A chymostatin-sensitive angiotensin II-generating enzyme was found in human gastroepiploic arteries. The enzyme was purified using heparin affinity and gel filtration columns. The molecular mass of the purified enzyme was 30 kDa, and the optimum pH was between 7.5 and 9.0. Enzyme activity was inhibited by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride and chymostatin, but not by ethylenediaminetetraacetic acid, pepstatin and aprotinin. The enzyme rapidly converted angiotensin I to angiotensin II (K(m), 67 mumol/l; Vmax, 43 pmol/s, kcat, 65/s), but did not hydrolyse angiotensin II, substance P, bradykinin, vasoactive intestinal peptide, luteinizing hormone-releasing hormone, somatostatin and alpha-melanocyte-stimulating hormone. The N-terminal sequence was identical to the sequence for human skin/heart chymase. Thus, the chymostatin-sensitive angiotensin II-generating enzyme in human vascular tissues is identified as chymase.
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PMID:Characterization of chymase from human vascular tissues. 935 25

Whereas oral or intraduodenal ethanol causes a moderate stimulation of pancreatic bicarbonate and enzyme output, intravenous ethanol inhibits basal and hormonally stimulated pancreatic exocrine secretion in humans, dogs, cats, pigs, rabbits, and rats. This inhibition could be mediated by inhibitory cholinergic mechanisms or be the result of a direct cellular effect of ethanol. In vitro investigations have specified several signaling molecules that may be involved in the action of ethanol on stimulus-secretion coupling in the exocrine pancreas, including cyclic adenosine monophosphate, intracellular calcium, and cholecystokinin and somatostatin receptors. In difference to pure ethanol solutions and distilled spirits, beer strongly stimulates pancreatic enzyme output, probably by nonalcoholic fermentation products. During chronic alcoholism, the ethanol-induced inhibition is replaced by an enhanced enzyme output that causes intraductal protein precipitation. In vitro investigations suggest that this increase is reversible after alcohol withdrawal. The occurrence of protein precipitates is considered to be a crucial step in the development of chronic alcoholic pancreatitis in humans. Other ethanol-induced secretory alterations that may contribute to the development of alcoholic pancreatitis are a decreased secretion of trypsin inhibitor, an increased cholinergic tone, and changes in the concentration of lithostathine.
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PMID:A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro. 980 44

Tryptase purified from rat and dog tissues has been reported, although the characteristics of these enzymes are different from human tryptase. For pathophysiological studies of human tryptase, studies on species that have a similar tryptase to humans is needed. In this study, we purified monkey tryptase from cheek pouch vascular tissues using heparin affinity and gel filtration columns. The monkey tryptase, which had a molecular weight of 130 kDa by gel filtration, consisted of a tetramer of 33 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The N-terminal sequence showed high homology with tryptases from other species. The optimum pH and temperature were 7.5-9.0 and 25-40 degrees C, respectively. The enzyme was labile in high-KCl buffer, and the optimum KCl concentration was 0.1 M. The enzyme activity was completely inhibited by diisopropyl phosphorofluoridate and leupeptin but not by soybean trypsin inhibitor and alpha-antitrypsin. The enzyme hydrolyzed vasoactive intestinal peptide but did not affect angiotensin I, somatostatin and bradykinin. In the present study, we first isolated monkey tryptase from cheek pouch vascular tissues and showed that the characteristics of monkey tryptase are very similar to those of human tryptase.
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PMID:Characteristics of monkey tryptase purified from cheek pouch vascular tissues. 1120 8

Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue ERp57 work together to help fold nascent polypeptides with glycans located toward the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack glycans or have sugars toward the C-terminus. In this study, we show that the PDI homologue PDILT is expressed exclusively in postmeiotic male germ cells, in contrast to the ubiquitous expression of many other PDI family members in the testis. PDILT is induced during puberty and represents the first example of a PDI family member under developmental control. We find that PDILT is not active as an oxido-reductase, but interacts with the model peptide Delta-somatostatin and nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone activity. In vivo, PDILT forms a tissue-specific chaperone complex with the calnexin homologue calmegin. The identification of a redox-inactive chaperone partnership defines a new system of testis-specific protein folding with implications for male fertility.
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PMID:A developmentally regulated chaperone complex for the endoplasmic reticulum of male haploid germ cells. 1750 49

To investigate the effects of oral administration of a trypsin inhibitor (TI), normal Wistar rats were fed a TI derived from squid (Todarodes pacificus) for 10 weeks and gene expression profiles in the duodenum, pancreas, liver, and muscle were then analyzed using DNA microarrays. Although no significant changes could be observed in growth, food intake, tissue weight, or blood tests among the tissues tested, the duodenum showed the most remarkable changes in the global gene expression profile. Significant up-regulation of mRNAs encoding gastrin, gastrokine, cholecystokinin and somatostatin in the duodenum was validated by qPCR analysis. In gene ontology (GO) analysis of the up-regulated differentially expressed genes (DEGs), GO terms related to keratinization and innate mucosal defense were enriched (p < 0.001) in the category of biological processes in addition to assumable terms such as regulation of secretion and response to nutrients, vesicle-mediated transport, and so forth. In the same analysis, calcium ion binding was listed at the deepest hierarchy in the category of molecular function. These results indicate that the duodenum responds to TI treatment by a wider range of physiological processes than previously assumed such as keratinocyte differentiation and innate mucosal defense, in which calcium plays a crucial role.
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PMID:Transcriptome analysis of the duodenum in Wistar rats fed a trypsin inhibitor derived from squid viscera. 2176 37


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