OBJECTIVES: Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR). METHODS: Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg·d) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg·d), taking WistarKyoto(WKY) as normal control (=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR. RESULTS: After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (<0.05). CONCLUSIONS The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.
Amlodipine ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Benzazepines ; pharmacology ; Blood Pressure ; Hypertension ; drug therapy ; Male ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Secretin ; metabolism ; Somatostatin ; metabolism

There are increasing number of cases of serum amylase and lipase levels being examined as part of health screening, but the clinical significance of these amylase and lipase levels is unclear. When the clinicians encounter patients with elevated pancreatic enzymes, the most common causes such as acute pancreatitis, hepatic or renal dysfunction should be ruled out first by thorough history taking, physical examination, and laboratory tests. Further tests including abdominal ultrasonography or computed tomography, lipid profile, tumor marker, isoenzyme, and calculation of amylase-to-creatinine clearance ratio or polyethylene glycol precipitation test should be performed to exclude other causes. If the pancreatic enzymes are continuously elevated through repeated tests without any apparent etiology, the diagnosis is made with chronic non-pathological pancreatic hyperenzymemia (CNPH). Magnetic resonance cholangiopancreatography is very useful and important modality for the patients with CNPH but the clinical significance of magnetic resonance cholangiopancreatography with secretin stimulation is still unclear. They can be evaluated through endoscopic ultrasonography with preference but it is less suitable for follow-up. Individualized approaches should be made after considering the need for active treatment or periodic follow-up for the benign pancreatic diseases associated with CNPH. It is difficult to conclude until more long-term data are reported because there are only limited number of researches and consensus on the range of tests to be performed for diagnosis, clinical significance of benign findings and end of follow-up in patients with CNPH.
Amylases ; Cholangiopancreatography, Magnetic Resonance ; Consensus ; Diagnosis ; Endosonography ; Follow-Up Studies ; Humans ; Hyperamylasemia* ; Lipase ; Mass Screening ; Pancreas ; Pancreatic Diseases ; Pancreatitis ; Physical Examination ; Polyethylene Glycols ; Secretin ; Ultrasonography

Secretin, a gastrointestinal peptide, has been found to be expressed in mouse endometrial stromal cells (mESCs) during early pregnancy. In order to further investigate the function of secretin during embryo implantation, the expression levels of secretin, secretin receptor, cytosolic phospholipase A(cPLA) and membrane prostaglandin E synthase 1 (mPGEs-1) were detected in the mice uterus from day 4 to 8 of pregnancy by real-time PCR, ELISA and in situ hybridization. mESCs isolated and cultured from day 4 of pregnancy were transfected with secretin expression vectors or treated with H89, a PKA inhibitor. Then the expression levels of cPLA, mPGEs-1 and cAMP responsive element-binding protein (CREB) were detected by real-time PCR and Western blot. The concentration of prostaglandin E2 (PGE) in the supernatant was determined by ELISA. The result showed that secretin, cPLAand mPGEs-1 mRNA expression increased gradually in implantation sites from day 5 to day 7 of pregnancy with the same tendency. The secretin levels in serum were significantly higher on days 6, 7 and 8 of pregnancy than that on day 5 of pregnancy. The concentration of secretin was significantly higher in implantation sites on days 6, 7 than that in non-implantation site on day 5. Transfection of secretin expression vector promoted cPLA, p-cPLAand mPGEs-1 expressions in mESCs, but not PGElevel in the supernatant. H89 could effectively inhibit the expression of CREB, p-CREB, p-cPLAand cPLAinduced by secretin. The results showed that the increased secretin expression in mESCs during embryo implantation may promote p-cPLA, cPLAand mPGEs-1 expression, and the promotion may be through PKA signaling pathway.
Animals ; Blotting, Western ; Cyclic AMP Response Element-Binding Protein ; Dinoprostone ; Female ; Mice ; Phospholipases A2, Cytosolic ; Pregnancy ; Prostaglandin-E Synthases ; Real-Time Polymerase Chain Reaction ; Secretin ; Stromal Cells ; Uterus

Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.
Autistic Disorder* ; Child ; Autism Spectrum Disorder* ; Critical Period (Psychology) ; Diagnosis ; Humans ; Maternal Behavior ; Naltrexone ; Oxytocin* ; Parents ; Pathology ; Polymorphism, Single Nucleotide ; Secretin ; Social Change ; Biomarkers

In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study.
Acetylcholine ; Behavioral Symptoms ; Chelating Agents ; Child ; Autism Spectrum Disorder* ; Complementary Therapies ; Diagnostic and Statistical Manual of Mental Disorders ; Drug Therapy* ; Glutamic Acid ; Oxytocin ; Pharmacogenetics ; Secretin ; Vitamins

The gastrointestinal functions of secretin have been fairly well established. However, its function and mode of action within the nervous system remain largely unclear. To gain insight into this area, we have attempted to determine the effects of secretin on neuronal differentiation. Here, we report that secretin induces the generation of neurite outgrowth in pheochromocytoma PC12 cells. The expressions of Tau and beta-tubulin, neuronal differentiation markers, are increased upon secretin stimulation. In addition, secretin induces sustained mitogen-activated protein kinase (MAPK) activation and also stimulates the cAMP secretion. Moreover, the neurite outgrowth elicited by secretin is suppressed to a marked degree in the presence of either PD98059, a specific MAPK/ERK kinase (MEK) inhibitor, or H89, a specific protein kinase A (PKA) inhibitor. Taken together, these observations demonstrate that secretin induces neurite outgrowth of PC12 cells through cAMP-MAPK pathway, and provide a novel insight into the manner in which secretin participates in neuritogenesis.
Animals ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Comparative Study ; Cyclic AMP/analysis/metabolism ; Enzyme-Linked Immunosorbent Assay ; Fluorescein-5-isothiocyanate ; Fluorescent Dyes ; Immunoblotting ; Immunohistochemistry ; Microscopy, Confocal ; Mitogen-Activated Protein Kinases/*metabolism ; Neurites/*drug effects ; Neurons/cytology/drug effects ; PC12 Cells ; Rats ; Research Support, Non-U.S. Gov't ; Reverse Transcriptase Polymerase Chain Reaction ; Secretin/*pharmacology

PURPOSE: This research was done to confirm the effect of secretin on pepsin secretion and to study whether or not feeding can depress the secretin-stimulated pepsin secretion (SSPS) with its related factors. METHODS: Heidenhain (HP) and Pavlov pouches (PP) were made in 6 dogs and cannulae were then inserted into the pouches. The fluids were collected through the cannula every 10 minutes for 3 hours in various conditions, including resting, feeding, secretin perfusion, acidification of the stom-ach and, gastric distension. A modified Anson's hemoglobin method was used to check the amount of pepsin. RESULTS: When secretin was perfused in the HP, there was no increase of pepsin secretion at 0.1 and 0.2 CU/kg/hr, but the pepsin secretion increased at 0.4 and 1.0 CU/kg/hr. Compared to the control, ANOVA showed significant differences for secretin 0.4 CU/kg/hr (P<0.01) and for secretin 1.0 CU/kg/hr (P<0.001). When milk was administered through the gastric cannula after secretin stimulation, pepsin production increased in the PP, but pepsin secretion in the HP dropped close to the basal level after administering milk. This depression was not related to acidity of the milk. ANOVA showed significant differences for secretin with milk vs milk alone (P<0.0005) and vs secretin alone (P<0.0025). The inhibition of SSPS was not observed with any gastric distension or acid perfusion. CONCLUSION: In the HP, secretin increased the pepsin secretion and the vagus nerve has an inhibitory effect on pepsin secretion under secretin stimulation. Milk feeding depressed the SSPS, and that depression was not related to pH of the food and gastric distension. Further study is needed in order to clarify the mechanism of depression.
Animals ; Catheters ; Depression ; Dogs ; Hydrogen-Ion Concentration ; Milk ; Pepsin A* ; Perfusion ; Secretin* ; Vagus Nerve

BACKGROUND/AIMS: The quantitative analysis of fecal elastase-1 has been proposed as a noninvasive test for the examination of pancreatic exocrine function. Therefore, we evaluated the diagnostic value of fecal elastase-1 by comparing with endoscopic intraductal secretin test (IDST) which is used as a direct exocrine function test for the diagnosis of chronic pancreatitis. METHODS: Fecal elastase-1 concentrations were measured by ELISA in spot stool samples of 40 healthy control subjects, 21 patients with liver disease, and 12 patients with chronic pancreatitis diagnosed with endoscopic retrograde cholangiopancreatography (ERCP) and IDST. Chronic pancreatitis were then sub-classified into mild (I), moderate (II) and severe form (III), using the Cambridge classification according to ERCP finding. The linear regression analysis to evaluate the correlation between the concentration of fecal elastase-1 and IDST was performed during ERCP. The cut-off value of fecal elastase-1 to discriminate chronic pancreatitis was calculated based on receiver operating characteristic curve, and the clinical usefulness of fecal elastase-1 in the diagnosis of chronic pancreatitis was evaluated. RESULTS: There were several significant correlations between fecal elastase-1 and various parameters of IDST: pancreatic juice secretory volume (r=0.797, p<0.002), bicarbonate concentration (r=0.846, p<0.001), elastase-1 concentration in pancreatic juice (r=0.671, p<0.017), and amylase output (r=0.783, p<0.003). The mean value of fecal elastase-1 concentration in the patients with chronic pancreatitis (197+/-77microgram/g stool) was significantly lower than those in the healthy control subjects (815+/-133microgram/g stool) and patients with liver disease (594+/-206microgram/g stool) (p<0.05). The cutoff value of fecal elastase-1 to discriminate between the healthy control and chronic pancreatitis patients was 201microgram/g stool. With this cutoff value, the accuracy, sensitivity, and specificity of fecal elastase-1 to diagnose chronic pancreatitis were 78.8%, 67.7%, and 82.5%, respectively, compared to the morphological severity (the sensitivity of mild, moderate, and severe chronic pancreatitis was 33.3%, 66.7%, 83.3%, respectively). CONCLUSIONS: Measurement of fecal elastase-1 is a reliable and sensitive non-invasive test for the diagnosis of moderate to severe forms of chronic pancreatitis.
Amylases ; Cholangiopancreatography, Endoscopic Retrograde ; Classification ; Diagnosis* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Linear Models ; Liver Diseases ; Pancreatic Function Tests* ; Pancreatic Juice ; Pancreatitis, Chronic* ; ROC Curve ; Secretin ; Sensitivity and Specificity

To clarify the roles of gonadal steroids on pancreatic exocrine secretion, effects of progesterone and estradiol-17beta on spontaneous and secretagogue-induced exocrine response of isolated perfused rat pancreas were investigated. Intra-arterial infusion of progesterone resulted in significant increase of the spontaneous pancreatic fluid and amylase secretion dose-dependently. However, estradiol-17beta did not exert any influence on spontaneous pancreatic exocrine secretion. Exogenous secretin, cholecystokinin (CCK), and acetylcholine markedly stimulated pancreatic fluid and amylase secretion. Progesterone initially enhanced secretin-induced amylase secretion, but this stimulatory response declined thereafter to basal value. Moreover, secretin-induced fluid secretion was not affected by infusion of progesterone. Therefore, initial increase of secretion-induced amylase secretion by progesterone seems to be a non-specific action by washout effect of secretin. Estradiol-17beta failed to change the secretin-induced fluid and amylase secretion. Both progesterone and estradiol-17beta did not exert any influence on CCK-induced fluid and amylase secretion. Acetylcholine-induced exocrine secretion of isolated perfused pancreas also was not affected by intra-arterial infusion of progesterone or estradiol-17beta. It is concluded from the above results that progesterone could enhance the spontaneous pancreatic fluid and amylase secretion of isolated perfused rat pancreas through non-genomic short- term action, and that these effects could be masked by more potent stimulants such as secretin, CCK, and acetylcholine.
Acetylcholine ; Amylases ; Animals ; Cholecystokinin ; Estradiol ; Gonads* ; Infusions, Intra-Arterial ; Masks ; Pancreas* ; Progesterone ; Rats* ; Secretin ; Steroids*

gamma-Aminobutyric Acid (GABA) is contained in pancreatic islet beta-cells although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA (10, 30 and 100micromol/kg/h), given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA (30micromol/kg/h) also further increased the amylase secretion stimulated by CCK+(30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA (10, 30 and 100micromol/kg/h) also dose-dependently elevated pancreatic amylase secretion evoked by CCK+alone. Bicuculline (100micromol/kg/h), a GABAA-receptor antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK+plus secretin or CCK+alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via GABAA-receptors in anesthetized rats, which may account for elevating the action of CCK+released by sodium oleate.
Amylases* ; Animals ; Bicuculline ; Cholecystokinin ; gamma-Aminobutyric Acid* ; Islets of Langerhans ; Oleic Acid* ; Pancreas ; Rats* ; Secretin ; Sodium* ; Urethane ; Water