Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of the present studies was to identify and characterize the site of secretin action in the liver. Sections of normal and bile duct-ligated rat livers were used for in vitro 125I-secretin receptor autoradiography. Saturable binding was observed in both normal and bile duct-ligated livers but was much greater in the bile duct-ligated preparations. Binding was limited to biliary epithelium and the increased secretin binding observed in the ligated livers correlated with the increase in ductular tissue. Saturable binding was inhibited in a dose-dependent fashion by increasing concentrations of nonradioactive secretin. Analysis of saturation binding showed that 125I-secretin binding was best fit by a one-site receptor model with a Kd of 5.3 +/- 1.1 nmol/L. Glucagon, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, growth hormone-releasing hormone, and cholecystokinin did not inhibit saturable 125I-secretin binding at concentrations of 1 pmol/L to 1 mumol/L. The authors conclude that high-affinity, specific secretin binding sites are present in rat intrahepatic biliary epithelium. When bile ducts are stimulated to proliferate by bile duct ligation, secretin binding is also increased.
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PMID:Localization and characterization of secretin binding sites expressed by rat bile duct epithelium. 153 32

We have documented and characterized the down-regulation of the 125I-secretin binding sites and the associated desensitization of the secretin receptor-cAMP system in rat gastric glands. Secretin induced a rapid decrease of the high-affinity 125I-secretin binding sites with t1/2 = 30 min at 37 degrees C. Half-maximal down-regulation and desensitization occurred at 10(-9) M secretin, a physiological concentration corresponding to the half-maximal activation of the secretin receptor. The Scatchard parameters of the low-affinity 125I-secretin binding sites were unaffected by the pretreatment. This desensitization is heterologous in view of the loss of responsiveness to the truncated glucagon-like peptide 1 (TGLP-1), and pharmacologically selective since the secretin-related analogue VIP (10(-7) M) does not alter the secretin-induced cAMP generation in rat gastric glands. The glycoprotein nature of the secretin receptor has also been demonstrated using WGA-agarose affinity chromatography of the solubilized 125I-secretin receptor complex.
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PMID:Functional and structural characterization of the secretin receptors in rat gastric glands: desensitization and glycoprotein nature. 165 Jun 11

Secretin, a gut-brain peptide, elicited cyclic AMP production in a clone of neuroblastoma cells derived from the C1300 mouse tumor. Adenylate cyclase (EC 4.6.1.1) in plasma membranes from these cells was stimulated by secretin greater than vasoactive intestinal peptide greater than peptide histidine isoleucine amide, but not by the related peptides glucagon, gastric inhibitory polypeptide, or human growth hormone releasing factor. Hill coefficients for stimulation approximated one and the response to submaximal peptide concentrations was additive, as expected for hormones competing for a single receptor associated with the enzyme. Binding of 125I-labeled secretin to the neuroblastoma plasma membranes was saturable, time-dependent, and reversible. The KD determined from kinetic and equilibrium binding studies approximated 1 nM. The binding site displayed marked ligand specificity that paralleled that for stimulation of adenylate cyclase. The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin. These findings demonstrate the functional association of the secretin receptor with adenylate cyclase in neuronally derived cells.
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PMID:Secretin receptors on neuroblastoma cell membranes: characterization of 125I-labeled secretin binding and association with adenylate cyclase. 632 61

Secretin is a gastrointestinal hormone responsible for the regulation of bicarbonate, potassium ion and enzyme secretion from the pancreas. A cDNA encoding the human secretin receptor was isolated from a human pancreatic adenocarcinoma cell-line cDNA library using polymerase chain reaction and library screening techniques. The cDNA isolated is 1717 bp in length encoding a 440 amino acid long polypeptide. Computer analysis of the receptor indicated that it is a member of the glucagon-VIP-secretin receptor family and is a G-protein coupled receptor containing seven hydrophobic transmembrane domains. The receptor was subsequently expressed in COS-7 cells and was able to bind specifically to human secretin with high affinity as indicated by the competitive displacement assay. The human secretin receptor was found to be functionally coupled to the stimulation of adenylyl cyclase resulting in the accumulation of intracellular cAMP in a dose-dependent manner. By Northern blot analysis, a 1.8 Kb mRNA was detected in human pancreas and intestine, while weak hybridization signals were detected in human colon, kidney and lung. Functional characterization of this receptor should enhance our understanding of the physiology and pathophysiology of human secretin, its structure-function, receptor interaction and receptor tissue distribution.
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PMID:Molecular cloning and functional characterization of a human secretin receptor. 761 8

Secretin is a 27-amino acid neuroendocrine peptide that stimulates fluid and electrolyte secretion in the gastrointestinal tract, activates tyrosine hydroxylase activity in the central nervous system, and affects cardiac and renal function. Specific receptors for secretin have been previously characterized on neuroblastoma cells, pancreatic acini, gastric glands, and liver cholangiocytes. We report here the isolation of a 1616-base pair cDNA from human lung tissue that encodes a 440-amino acid, 50-kDa, G protein-coupled human secretin receptor (HSR), with homology of 80% with the rat secretin receptor and 37% with the human type I vasoactive intestinal peptide receptor. Northern blot analysis of human tissue mRNA revealed that the relative intensity for expression of a 2.1-kilobase HSR transcript was pancreas > kidney > small intestine > lung > liver, with trace levels in brain, heart, and ovary. Stable transfectants of HSR in human embryonic kidney 293 cells, termed 293S12, expressed 10(5) binding sites/cell for 125I-secretin, with an apparent Kd of 3.2 nM. Vasoactive intestinal peptide, pituitary adenylyl cyclase-activating peptide-38, and glucagon were less potent (by 3 orders of magnitude) than secretin in competitively inhibiting 125I-secretin binding to 293S12 cells. Secretin evoked concurrent dose-dependent increases in intracellular cAMP and calcium levels in 293S12 cells and stimulated a 4-fold increase in phosphatidylinositol hydrolysis. Thus, the HSR expressed by stable transfectants can couple to two distinct intracellular signaling pathways.
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PMID:Molecular cloning and expression of a human secretin receptor. 770 Feb 44

A cDNA encoding a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor was cloned from a bovine brain cDNA library using a synthetic oligonucleotide probe corresponding to the partial N-terminal amino acid sequence of the PACAP receptor purified from the bovine brain. The cloned cDNA encoded a polypeptide of 513 amino acid residues with seven putative transmembrane domains. The deduced amino acid sequence exactly matched the N-terminal amino acid sequence of the purified PACAP receptor. It also shared an apparent similarity with the vasoactive intestinal peptide (VIP), secretin, growth hormone releasing hormone, calcitonin, and glucagon receptors, suggesting that the PACAP receptor is a member of the secretin receptor subfamily of the guanine nucleotide-binding regulatory protein-coupled receptor family. Northern blot analysis showed that the size of the major mRNA band which hybridized with the cDNA was about 7 kb in the bovine cerebral-cortex and hippocampus. An expression vector containing the cloned cDNA for the PACAP receptor was introduced into Chinese hamster ovary (CHO) cells. The affinity of PACAP receptors expressed on the transfected CHO cells was quite similar to that of natural PACAP receptors on the bovine brain membranes. Competitive binding experiments showed that PACAP38 displaced the binding of 125I-labeled PACAP27 to the receptors on the CHO cells more efficiently than PACAP27, while VIP was less effective. In addition, both of PACAP27 and PACAP38 elevated the levels of cAMP and inositol phosphates in the transformed CHO cells. These results indicate that the PACAP receptors encoded by the cloned cDNA are identical to the purified PACAP receptors, and that they can stimulate dual signaling cascades.
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PMID:Cloning and expression of a complementary DNA encoding the bovine receptor for pituitary adenylate cyclase-activating polypeptide (PACAP). 804 55

A cDNA fragment was PCR amplified at low-stringency from rat DNA, using two degenerated primers corresponding to consensus sequences in the second and third transmembrane segments of members of the secretin receptor family. A synthetic oligodeoxynucleotide based on the 3 end of this fragment, when used in Northern-blot analysis, hybridized to a broad 1.5-3.0 kb band in rat liver. It was then used as a probe for screening a cDNA library generated from size-fractionated rat liver poly(A)+ RNA. Overlapping alignment of sequences from 3 clones identified a 1455 residue open reading frame encoding a 485 amino acid peptide showing 7 putative transmembrane segments and 42% identity with the glucagon-like peptide 1 (GLP-1) receptor. In addition, four small (85-300 bp) introns were variously represented in the isolated clones.
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PMID:Small introns in a hepatic cDNA encoding a new glucagon-like peptide 1-type receptor. 838 42

Frozen sections of the rat stomach were incubated with 125I-labeled porcine secretin, and then secretin binding sites were localized by autoradiography. Saturable binding was observed only in the muscularis externa (circular and longitudinal smooth muscle layers) of the proximal nonglandular forestomach. Saturable binding was quantitated by densitometry. 125I-porcine secretin bound to a single class of high-affinity binding sites with a dissociation constant of 0.6 nM. Porcine and rat secretins were nearly equipotent in inhibiting saturable 125I-porcine secretin binding, and vasoactive intestinal polypeptide, peptide histidine-isoleucine, and glucagon were much weaker. Carbachol (100 microM) stimulated a sustained increase in tension in forestomach muscle in vitro, and porcine secretin caused relaxation of this stimulated contraction. We conclude that rat forestomach smooth muscle expresses a high-affinity specific secretin binding site that mediates relaxation. This putative secretin receptor may mediate some of the actions of secretin on gastric motility.
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PMID:Secretin receptors mediating rat forestomach relaxation. 849 12

Gastric inhibitory polypeptide (GIP), which is released from the gastrointestinal tract, stimulates insulin secretion from pancreatic beta cells and plays a crucial role in the regulation of insulin secretion during the postprandial phase. We have isolated the human gene (GIPR) and cDNA encoding the GIP receptor by a combination of the conventional screening and polymerase chain reaction procedures. Human GIP receptor cDNA encodes a protein of 466 amino acids that is 81.5 and 81.2% identical to the previously cloned hamster and rat GIP receptor, respectively. Hydropathic analysis shows the presence of a signal peptide and seven potential transmembrane domains, a feature characteristic of the VIP/glucagon/secretin receptor family of G protein-coupled receptors. The human GIPR gene is about 13.8 kb long, consists of 14 exons, and carries 17 Alu repeats.
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PMID:Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA. 857 74

The genomic organization of the human gene encoding the receptor for glucagon-like peptide-1 (GLP-1 (7-37)/(7-36) amide) was analyzed to reveal the relationship to other G-protein-coupled receptors. The coding sequence of the GLP-1 receptor is interrupted by 12 introns. These introns are uniformly distributed within the open reading frame. The length of the introns varies between 6.6 kb and 100 bp, in contrast to the relative constant length of 100 bp of the exons. All of the exon/intron splice junctions characterized followed the consensus GT-AG rule. A comparison of the genomic structure with other related receptor genes indicates that the exon/intron organization is well-conserved among the VIP/ glucagon/secretin receptor family.
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PMID:The genomic organization of the human GLP-1 receptor gene. 979 62


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