Disease relevance of Sctr

• SR-retargeted adenovirus transduced SR-expressing cells at more than sixfold higher levels than adenovirus alone [1].
• Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR showed that secretin receptor mRNA is expressed in the nodose ganglia and levels were higher in the right compared with the left ganglion [2].
• 1. The present study investigated the role of second messenger-dependent protein kinase A (PKA) and C (PKC) in the regulation of endogenous secretin receptor responsiveness in NG108-15 mouse neuroblastomaxrat glioma hybrid cells [3].
• Hemagglutinin epitope-tagged wild-type rat secretin receptor construct was expressed using the recombinant baculovirus/Sf9 insect cell-based system, achieving a level of expression substantially higher than that previously achieved in Chinese hamster ovary (CHO-SecR) cells [4].

High impact information on Sctr

• AE-2 gene expression was unaffected by proinflammatory cytokines, whereas CFTR and SR expression was increased [5].
• Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels [6].
• The secretin receptor expressed in COS cells could specifically bind the iodinated secretin with high and low affinities [7].
• A complementary DNA encoding the rat secretin receptor was isolated from a CDM8 expression library of NG108-15 cell line [7].
• However, the amino acid sequence of the secretin receptor has no significant similarity with that of other G protein-coupled receptors [7].

Biological context of Sctr

• The nucleotide sequence analysis of the cDNA has revealed that the secretin receptor consists of 449 amino acids with a calculated Mr of 48,696 [7].
• In the present study, we determined the disulfide bonding pattern of the prototypic class B secretin receptor by applying the same paired cysteine mutagenesis approach and confirming the predicted bonding pattern with proteolytic cleavage of intact functional receptor [8].
• Agonist-stimulated phosphorylation of the carboxyl-terminal tail of the secretin receptor [9].
• This probe specifically bound to the secretin receptor with high affinity (IC50 = 13.2 +/- 2.5 nM) and was a potent stimulant of cAMP accumulation in secretin receptor-bearing Chinese hamster ovary-SecR cells (EC50 = 720 +/- 230 pM) [10].
• Upregulation of secretin receptor gene expression in rat cholangiocytes after bile duct ligation [11].

Anatomical context of Sctr

• Co-expression of the secretin receptor with the alpha-subunit of rat Gs protein increased the concentration of the high affinity receptor in the membrane fraction of the transfected COS cells [7].
• RT-PCR of lymphocyte mRNA from spleen and thymus identified secretin and secretin receptor transcripts [12].
• The expression of secretin receptor gene and secretin-induced cAMP levels and secretin-induced bicarbonate-rich choleresis increased during the period of bile duct renewal [13].
• These results support the existence of a secretin receptor subtype mediating inhibition of gastric acid secretion that is distinct from the previously characterized pancreatic secretin receptor [14].
• By immunocytochemical staining, secretin is localized in the principal cells of the initial segment and caput epididymidis, whereas secretin receptor is present in the principal cells of the proximal as well as the distal part of the epididymis [15].

Associations of Sctr with chemical compounds

• The secretin receptor is prototypic of the class II family of G protein-coupled receptors, with a long extracellular amino-terminal domain containing six highly conserved Cys residues and one Cys residue (Cys(11)) that is present only in the most closely related family members [16].
• These data suggest that secretin receptors in the rat brain may be coupled to adenylate cyclase in a stimulatory manner and that secretin-(5-27) may function as a central secretin receptor antagonist [17].
• Furthermore, treatment with the protein synthesis inhibitor cycloheximide produced a time-dependent increase in secretin receptor responsiveness [3].
• 2. In whole cell cyclic AMP accumulation studies, activation of PKC either by phorbol 12-myristate 13-acetate (PMA) or by purinoceptor stimulation using uridine 5'-triphosphate (UTP) decreased secretin receptor responsiveness [3].
• Different actions of secretin and Gly-extended secretin predict secretin receptor subtypes [14].

Physical interactions of Sctr

• 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 [18].

Regulatory relationships of Sctr

• [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 [19].
• In vitro, somatostatin inhibited SR gene expression and secretin-induced cAMP synthesis only in large cholangiocytes [20].

Other interactions of Sctr

• ET-1 inhibits secretin-induced ductal secretion by decreasing secretin receptor and cAMP synthesis, two important determinants of ductal secretion [21].
• Amino acids 8, 13, and 15 of the PACAP molecule contributed significantly to the low affinity of PACAP for the secretin receptor [22].
• We isolated pure cholangiocytes from normal and BDL rats and assessed gastrin effects on secretin receptor (SR) gene expression and intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels [23].
• It may be suggested that there is a kind of "cross-talk," between the adenylate cyclase system, that is, the secretin receptor, and carbachol or CCK-8 receptor [24].
• Amino acid residues 103-117 and 126-137 in the extracellular N-terminal tail and residues 206-219 and 220-231 in the first extracellular loop of the glucagon receptor were replaced with the corresponding segments of the glucagon-like peptide-1 receptor or the secretin receptor [25].

Analytical, diagnostic and therapeutic context of Sctr

• Molecular cloning and expression of a cDNA encoding the secretin receptor [7].
• Peptide mapping using proteolytic cleavage, immunoprecipitation, and radiochemical sequencing identified that each of these three probes labeled the amino terminus of the secretin receptor [26].
• In the present study, the localization of secretin receptor was investigated in the rat brain by using an in vitro autoradiography technique [27].
• The glycoprotein nature of the secretin receptor has also been demonstrated using WGA-agarose affinity chromatography of the solubilized 125I-secretin receptor complex [28].
• Several treatments, including vagal ligation, vagotomy, perivagal application of capsaicin or colchicine, intravenous infusion of tetrodotoxin, and intraperitoneal injection of atropine, were performed to investigate their effects on secretin receptor binding to forestomach membranes [29].

References