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Concurrent and independent HCO3- and Cl- secretion in a human pancreatic duct cell line (CAPAN-1).

The present study investigated both HCO-3 and Cl- secretions in a human pancreatic duct cell line, CAPAN-1, using the short-circuit current (Isc) technique. In Cl-/HCO-3-containing solution, secretin (1 microM) or forskolin (10 microM) stimulated a biphasic rise in the Isc which initially reached a peak level at about 3 min and then decayed to a plateau level after 7 min. Removal of external Cl- abolished the initial transient phase in the forskolin-induced Isc while the plateau remained. In HCO-3/CO2-free solution, on the contrary, only the initial transient increase in Isc was prominent. Sum…

Enzymatic maturation of the gastrointestinal tract and its relevance to food allergy and intolerance in infancy.

The biologic clock that determines the temporal sequence of maturation of digestive and absorptive processes in the gastrointestinal tract is genetically predetermined, but may be modified by dietary, hormonal, or other factors. In general it may be said that the gastrointestinal tract of full-term neonates is capable of digesting and absorbing a nutritionally adequate quantity of dietary protein but capacity is limited. Very low birth weight preterm infants, who are surviving the early neonatal period in increasing numbers, have immaturity of a wide range of digestive and membrane-associated

Cell-cell interaction underlies formation of fluid in the male reproductive tract of the rat.

The epithelia lining the epididymides of many species consists of several cell types. We have provided evidence that the basal cells are essential to the integrated functions of the epithelium. Basal cells, but not principal cells, and other cells in the epididymis express TRPC3 and COX-1. We have isolated basal cells from intact rat epididymis using antibody-coated Dynabeads and subjected them to whole-cell patch-clamp measurement of nonselective cation channel activity, a feature of TRPC3 protein, and Fluo-3 fluorescence measurement of intracellular Ca2+ concentration. The results show that

INTESTINAL OBSTRUCTION : I. A STUDY OF A TOXIC SUBSTANCE PRODUCED IN CLOSED DUODENAL LOOPS.

Closed duodenal loops may be made in dogs by ligatures placed just below the pancreatic duct and just beyond the duodenojejunal junction, to … ut applied locally or given intravenously it causes no bleaching of the engorged intestinal mucosa. Secretin is not found in the duodenal loop fluid, and the loop material does not influence the pancreatic secretion. Intraportal injection of the toxic material gives a reaction similar to intravenous injection. Intraperitoneal and subcutaneous injections pr …

Endocrine paraneoplastic syndromes in lung cancer: A call for clinical vigilance (Review).

Endocrine paraneoplastic syndromes (PNS) are uncommon but clinically impactful manifestations associated with malignancies, particularly lung cancer, most notably small-cell lung cancer. These syndromes arise from ectopic hormone production by malignant cells, causing systemic effects that are independent of direct tumor invasion or metastasis. Their presentation often precedes or signals recurrence of the primary cancer, underscoring the importance of early recognition and targeted intervention. Common endocrine PNS in lung cancer include syndrome of inappropriate antidiuretic hormone secreti

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… The secretin stimulation test is often used to confirm the diagnosis; an abnormal rise in gastrin levels following secretin administration strongly suggests Zollinger-Ellison syndrome. … magnetic resonance imaging | Surgery, somatostatin analogs, GH receptor antagonists, addressing ectopic source Zollinger-Ellison syndrome | Gastrin | Ectopic production of gastrin causing hyper-secretion of gastric acid | Recurrent peptic ulcers, GERD, diarrhea, abdominal pain | Elevated fasting gastrin, secretin …

Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to … ty evidence, weak recommendation).When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation). 11 In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with lapa …

[Review of psychopharmacological treatments in adolescents and adults with autistic disorders].

Autism is an early developmental disorder. It leads to severe and durable disturbances. Given this problem, no treatment can be excluded a p … of drugs, vitamins or method used in autism after sporadic observations of their positive effects. Secretine: An important improvement has been reported in isolated cases. However, controlled studies in children do not confirm these results. Vitamines B6, B12 and Magnesium: An improvement in socialization and in behavioural disorders have been reported in …

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes sha

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… Second, although secretin, like vasopressin, activates adenylyl cyclase in the outer medulla and decreases urine output in wild-type and Brattleboro rats, genetic elimination of the secretin receptor and administration of exogenous secretin to PCK or PCK/Brattleboro rats or to Pkd2 -/WS25 mice did not … This may be because the internalization of the secretin receptor is unaffected by GRK mediated phosphorylation or by the expression of dominant negative β-arrestin ( Walker et al., 1999 ). Recruitment of β-arrestins to GPCRs after agonist activation is to large extent dependent on β/γ signaling. …

Accidental Ixazomib Overdose in a Patient With Multiple Myeloma.

Multiple myeloma is the second most common hematological malignancy. Ixazomib is the first oral proteasome inhibitor approved in the United States for the management of multiple myeloma who have received at least one prior treatment. The availability of oral chemotherapeutic agents for the management of multiple myeloma has made it easier for patients who do not have to come to the hospital for chemotherapy infusions. However, many barriers are associated with oral chemotherapy, and one of them is a misinterpretation of instruction which can have deleterious effects. In this case report, we pr

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… Octreotide is a somatostatin analog that inhibits intestinal hormones including serotonin, vasoactive intestinal peptide, secretin, motilin, and other pancreatic enzymes and regulates intestinal water and electrolyte balance causing net absorption. 8 There are no known renal or hepatic toxicities associated …

Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.

Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PA

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… The PACAP receptor family (part of the Secretin family) arose from the Adhesion receptor branch that regulate close contact local interactions [ 20 , 21 ]. … In addition, the secretin receptor also binds both PACAP and VIP with equal affinity and stimulates the same biological effect to the same extent as secretin, but the latter shows higher affinity [ 140 ]. …

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant cha

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… Current GPCR-Targeting Drugs GPCR is a tractable class of drug targets GPCRs are activated by a variety of ligands, including ions, hormones, neurotransmitters, proteins, and protons. 3 , 11 The human GPCR family has been classified into four subfamilies: class A (rhodopsin), B (secretin and adhesion … For example, in an animal model, drinking behavior was affected by inhibiting dimerization of the secretin receptor and AGTR1 using a peptide from transmembrane domain 4 (TM4). 43 The TM5/TM6 cannabinoid receptor (CB1R) peptide inhibits dimerization of the CB 1 R and serotonin receptor (5HT2AR) and is …

Cutaneous Squamous Cell Carcinoma Producing Granulocyte Colony-stimulating Factor and Parathyroid Hormone-related Protein: A Case Report and Literature Review.

We herein report a case of cutaneous squamous cell carcinoma (SCC) characterized by paraneoplastic hypercalcemia-leukocytosis syndrome. The patient presented with systemic symptoms, including anorexia, a fever, and a tumoral lesion on the upper arm. Laboratory test results revealed hypercalcemia and leukocytosis. A tissue biopsy confirmed SCC, and further investigation revealed elevated parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF) levels. Immunostaining demonstrated G-CSF production by the tumor cells. Radiation therapy was administered, which i

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… Esophageal small-cell carcinoma with ectopic production of parathyroid hormone-related protein (PTHrp), secretin, and granulocyte colony-stimulating factor (G-CSF). Dig Dis Sci 44: 1312-1316, 1999. 25. Kuroki M, Uto H, Ido A, et al. …

Историческое развитие иммуноэндокринных концепций психических расстройств и их терапии.

Отношения между центральной нервной, иммунной и эндокринной системами являются предметом психиатрических исследований, особенно в области депрессии и шизофрения. У поля длинные предтечи. Наблюдаемые явления, связанные с этими отношениями, восходят к неолитической эпохе. Теории иммуноэндокринной системы в самом широком смысле записаны в древности. В 19th Крепелин и Вагнер-Джаурег сообщили о первых клинических наблюдениях у пациентов психиатрических учреждений. Von Bestow, Эддисон и Кушинг описали психические симптомы у пациентов, страдающих эндокринными заболеваниями. :: 20th откровение века с

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… They called this agent “secretin” [ 39 ]. In 1905 Starling proposed “hormone” as the generic term for any messengers that are released by endocrine glands into the blood to stimulate the activity of organs, such as secretin. …

Декодирование связи между микроорганизмами и автоиммунизацией: многоаспектный обзор данных по конкретным патогенам, которые вызывают аутоиммунные заболевания.

Происхождение и прогрессирование аутоиммунных заболеваний (АИД) являются результатом совокупного воздействия генетической восприимчивости, дефектов иммунной реакции и экологических факторов. Среди них микроорганизмы, являющиеся ключевыми экологическими факторами, широко гипотезуют для того, чтобы сыграть свою роль в инициировании АИД, однако точная причинно-следственная связь еще не доказана. Цель этого обзора заключается в глубоком изучении ключевой роли конкретных микробных инфекций в инициировании АИД путем интеграции данных, полученных с помощью three - измерения: эпидемиологические исслед

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… Additionally, molecular mimicry between the nucleoprotein of influenza virus and the hypothalamic secretin receptor 2 is considered an important mechanism triggering narcolepsy [ 4 ]. These findings strongly suggest that microbial infections are key drivers of AID occurrence. …

Early detection of sporadic pancreatic cancer: summative review.

Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdiscipli

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… For example, it has been found that the prevalence of mutant GNAS in duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs is similar to that found in resected IPMNs, 92,93 suggesting that pancreatic juice is a reliable sample for detecting molecular alterations in the … Similarly, the detection of TP53 mutations in secretin-stimulated pancreatic juice samples was found to be a highly specific indicator of the presence of invasive PC or high-grade dysplasia. …

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs

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… In rats subjected to bile duct ligation, SST affects cholangiocytes choleretic activity, by counteracting the effect of secretin on the biliary excretion of water and bicarbonate by cholangiocytes, in cholestatic conditions [ 72 ]. … Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by cholangiocytes. Am J Physiol. 1995;269(1 Pt 1):G110–G118. doi: 10.1152/ajpgi.1995.269.1.G110. Catalan RE, Martinez AM, Araones MD. Evidence for a role of somatostatin in lipid metabolism of liver and adipose tissue. …

Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.

The G protein-coupled receptor Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations o

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… Human GPCRs are split into four classes based on structure and sequence similarity: A (rhodopsin), B (secretin), C (glutamate), and F (Frizzled). Class F consists of Smoothened (Smo) and 10 paralogues of Frizzled, which regulate the Hedgehog (Hh) and Wnt signalling pathways, respectively [ 2 ]. …

Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

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… Based on structural and sequence homology, GPCRs are classified into five families: rhodopsin (Family A, 672 members), secretin (Family B1, 15 members), adhesion (Family B2, 33 members), glutamate (Family C, 22 members), and frizzled/taste2 (Family F, 36 members) (Katritch et al. 2012 ; Hilger 2021 ) … In contrast, another study shows that CNV in GPCR: MRGPRX1 deletion, MC4R deletion, and neuropeptide SCT (secretin) amplification, which are found in neuroendocrine prostate cancer and pancreatic cancer, are highly dominant and can be considered as valuable markers for treatment and diagnosis (Zhao et …

G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.

G protein-coupled receptors (GPCRs) are the largest and most diverse class of membrane proteins, mediating cellular responses to a wide range of extracellular stimuli. GPCRs initiate complex intracellular signaling networks that regulate vital physiological functions and are associated with numerous diseases, including various types of cancer. Their conserved seven-transmembrane (7TM) structure enables these signaling networks by allowing interactions with multiple ligands and intracellular effectors. In several types of tumors, abnormal GPCR signaling promotes carcinogenesis by supporting imm

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… GPCRs are categorized into different classes based on similarities in the peptide chain patterns within the characteristic 7TM helical domains—the rhodopsin class (class A), secretin class (class B), adhesion class/glutamate class (class C), and frizzled/taste class (class F). … Class B GPCRs Class B GPCRs are categorized into B1 secretin receptors and B2 adhesion receptors. Class B1 GPCRs undergo a sequence of conserved conformational changes within their 7‐transmembrane domain. …