Disease relevance of Sct

• Secretin evokes catecholamine secretion from PC12 pheochromocytoma cells [1].
• Secretin-mediated gene delivery, a specific targeting mechanism with potential for treatment of biliary and pancreatic disease in cystic fibrosis [2].
• Ablation of secretin-expressing cells produced severe colitis with morphological features similar to those observed in graft-versus-host (GVH) disease [3].
• Secretin receptors were highly expressed in non-neoplastic ducts and lobuli and also in lower amounts in ductal neoplasias, including ductal adenocarcinoma, intraductal papillary mucinous tumors, and pancreatic intraepithelial neoplasia [4].
• Protective effects of exogenous secretin on ceruletide-induced acute pancreatitis in the rat [5].

Psychiatry related information on Sct

• Several clinical studies have reported modestly increased social interaction in autistic children following intravenous secretin administration [6].

High impact information on Sct

• The ACh-induced potentiation of the secretin effect on both intracellular cAMP levels and the Cl-/HCO3- exchanger activity was individually abolished by two calcineurin inhibitors, FK-506 and cyclosporin A (100 nM) [7].
• The effects of secretin on ion transport mechanisms involved in regulation of intracellular pH (pHi) and HCO3- excretion were characterized in bile duct epithelial (BDE) cells isolated from normal rat liver. pHi was measured with 2,7-bis(carboxy-ethyl)-5(6)-carboxy-fluorescein-acetomethylester (BCECF-AM) using a microfluorimetric method [8].
• Acoustic stress inhibited cholecystokinin-8 (CCK)- and meal-induced gallbladder contraction, and restraint stress inhibited basal and CCK/secretin-stimulated pancreatic secretion [9].
• To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas [10].
• In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin [10].

Chemical compound and disease context of Sct

• We conclude that GVH-like colitis in ganciclovir-treated Sec-HSVTK mice arises from depletion of secretin gene-expressing lymphoid cells and not from the failure of secretin production [3].
• The effect of secretin (0.4 C.U. per hr per 100 gm body weight) on bile flow and the apparent maximal hepatic transport of bilirubin (Tm) was investigated in the rat [11].
• The effect of the microtubule inhibitor colchicine on the ductular bile formation and HCO3- secretion induced by secretin was, therefore, explored in a secretin-responsive rat model characterized by marked hyperplasia of bile ductules [12].
• Secretin prevents taurocholate-induced intrahepatic cholestasis in the rat [13].
• Five gastro-entero-pancreatic hormones or related peptides (tetragastrin, glucagon, secretin, cholecystokinin-pancreozymin and cerulein) significantly increased the number of stomach cancer cells from 15% to 310% of the number of control cells cultivated in a serum-free, hormone-free medium [14].

Biological context of Sct

• Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels [15].
• Secretin also augmented (approximately 4-fold) phosphorylation of ERK1/2 [1].
• Consistent with the importance of this residue, alanine replacement mutagenesis (R14A) resulted in substantial reductions in the potency (127-fold) and binding affinity (400-fold) of secretin relative to its action at the wild-type receptor [16].
• The predicted amino acid sequences reveal that each precursor consists of a signal peptide, an N-terminal peptide, secretin, and a 72-amino acid C-terminal peptide [17].
• Comparison of the rat secretin gene to the other members of the glucagon-secretin gene family reveals that similarities are restricted to the exons encoding the biologically active peptides [18].

Anatomical context of Sct

• Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and (3)H-TC uptake in purified cholangiocytes [19].
• Secretin stimulated both endogenous CgA gene transcription (approximately 4-6-fold) as well as transfected CgA promoter activity (approximately 8-10-fold; EC50, approximately 7 nm) in PC12 cells [1].
• Sudden onset of colitis after ablation of secretin-expressing lymphocytes in transgenic mice [3].
• Immunoblot analysis of protein extracts from spleen and thymus identified secretin-like immmunoreactant [3].
• Though secretin mRNA was demonstrated in mouse lymphoid organs, its role in the immune system is unknown [3].

Associations of Sct with chemical compounds

• Colchicine ablated secretin pretreatment-dependent bile acid-induced choleresis, increased biliary lipid secretion, and the prolongation of the TC biliary transit [19].
• Phosphoamino acid analysis of the secretin phosphoreceptor demonstrated predominance of phosphothreonine over phosphoserine (3.2:1), with no phosphotyrosine observed [20].
• The unusually high number of serine, leucine, and arginine residues in secretin has precluded the use of oligonucleotides to screen cDNA libraries to isolate a secretin cDNA [17].
• Rat secretin differs from its porcine counterpart by a single glutamine-for-arginine substitution at position 14 [17].
• Second, we found that the previously reported facilitatory action of secretin on GABAergic inputs to Purkinje neurons is partly dependent on the release of endogenous glutamate [21].

Physical interactions of Sct

• Secretin is a 27-residue peptide hormone with a diffuse pharmacophoric domain that binds to the secretin receptor, a prototypic member of the Class B family of G protein-coupled receptors [22].
• Our results suggest that although the Gln(3) residue of glucagon did not interact with the equivalent binding pocket as the Asp(3) residue of vasoactive intestinal peptide or secretin, the Asp(3)-glucagon analogue was able to interact with position 188 of the K188R/I195K glucagon receptor [23].

Regulatory relationships of Sct

• We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores [19].
• ET-1 inhibits secretin-induced ductal secretion by decreasing secretin receptor and cAMP synthesis, two important determinants of ductal secretion [24].
• The inhibitory effects of ET-1 on secretin-induced cAMP synthesis and luminal duct expansion were blocked by specific inhibitors of the ETA (BQ-610) receptor [24].
• Simultaneous infusion of gastrin inhibited secretin-induced choleresis and bicarbonate output in BDL rats [25].
• [psi 4,5]Secretin was shown to be a secretin receptor antagonist that inhibits secretin-stimulated increase in adenosine 3',5'-cyclic monophosphate in isolated pancreatic acini of the guinea pig [26].

Other interactions of Sct

• In conclusion, secretin stimulates cholehepatic shunting of conjugated bile acids and is associated with increased cholangiocyte apical membrane ASBT [19].
• Secretin activation of chromogranin A gene transcription. Identification of the signaling pathways in cis and in trans [1].
• Trans-activation (approximately 21-fold) of GAL4-CREB fusion protein by secretin indicates involvement of CREB in secretin signaling to gene transcription [1].
• The amino acid sequence deduced from the shorter transcript is identical to a precursor form of secretin recently isolated from porcine duodenum [Gafvelin, G., Jornvall, H. & Mutt, V. (1990) Proc. Natl. Acad. Sci. USA 87, 6781-6785] [18].
• Recently, we found that, in isolated, vascularly perfused rat stomach model, the inhibition of acid secretion by pituitary adenylate cyclase activating polypeptide (PACAP) was mediated in part via local release of secretin [27].

Analytical, diagnostic and therapeutic context of Sct

• Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels [15].
• RT-PCR of lymphocyte mRNA from spleen and thymus identified secretin and secretin receptor transcripts [3].
• In the present study, a short cDNA encoding porcine secretin was amplified from duodenal mucosal first-strand cDNA template by using 16,384- and 4096-fold degenerate primers in the DNA polymerase chain reaction [17].
• Although secretin immunoreactivity has been localized in the central nervous system by some laboratories, we are unable to detect secretin mRNA in tissues of the central nervous system by Northern blot hybridization [17].
• Recent evidence suggests that intravenous infusion of secretin causes fos activation in NTS, a relay station playing important roles in the central regulation of autonomic functions [28].

References