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 ontogeny of oxytocin receptors in rat forebrain was studied using the selective oxytocin receptor antagonist 125I-d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29]OVT [( 125I]-OTA). With in vitro receptor autoradiography, binding wa noted on the first postnatal day in dorsal subiculum and thalamus. On postnatal days 5-18, intense labeling was evident in posterior cingulate cortex, dorsal subiculum, lateral septum, and the CA1 subfield of hippocampus. Of these regions only the lateral septum expressed oxytocin receptors in adult brain. Competition studies on coronal sections through posterior cingulate, septum, and dorsal subiculum at P10 demonstrated that transient binding sites in these areas were indeed oxytocin selective (OXY greater than AVP greater tha V1 greater than V2). Result of saturation studies on cingulate membranes from 10-day-old pups agreed favorably with previous reports of the kinetics of [125I]-OTA binding to adult oxytocin receptors (Kd = 0.1 nM in P10 cingulate cortex vs. 0.07 nM for adult ventral subiculum). In contrast to these evanescent developmental sites, oxytocin receptors in the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus only appeared in adulthood, presumably in response to the surge of gonadal steroids at puberty.
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PMID:Ontogeny of oxytocin receptors in rat forebrain: a quantitative study. 255 21

The fate of plasma glucagon has been analyzed in detail by Desbuquois and Postel-Vinay. The present work was carried out to clarify the relationships between plasma glucagon disappearance and its tissue uptake. For the purpose, we injected rats intravenously with 125I-glucagon alone or with concomitant or sequential injections of native glucagon. Plasma 125I-glucagon was analyzed by Biogel P10 chromatography. Liver and kidney glucagon kinetics were studied from the point of view of the evolution of the total radioactivity present in each tissue a few minutes after glucagon injection. 125I-glucagon was rapidly cleared from the plasma (half-life within 2 min); it was intensively associated with liver and kidneys. Liver radioactivity rapidly declined within the first 5 min after injection, whereas kidney radioactivity increased. The concomitant injection of increasing amounts of native glucagon with 125I-glucagon progressively reduced the liver radioactivity, indicating that glucagon was trapped in a saturable compartment. In contrast, kidney radioactivity remained unchanged. The sequential injection of 125I-glucagon and excess native glucagon resulted in a shift to the right in the plasma 125I-glucagon decay curve which suggests that the glucagon excess displaced 125I-glucagon from its distribution compartment back into the plasma. The compartment where glucagon uptake occurred a few minutes after 125I-glucagon injection displayed some of the fundamental properties of glucagon receptors, i.e. saturatibility and reversibility.
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PMID:Relationship between plasma glucagon disappearance and tissue uptake in rats. 370 5

A primary ovarian carcinoid composed of both trabecular and strumal types was studied by histochemical, immunocytochemical, and biochemical techniques. High contents of glucagon, secretin, and calcitonin were demonstrated in the tumor homogenate. All of the tumor cells, irrespective of histologic type, showed properties of argyrophilia and neurosecretory granules on electron microscopy. Glucagon-producing cells were positive in trabecular carcinoid by immunoperoxidase techniques. Bio-Gel P10 gel filtration showed that the molecular weight of major immunoreactive glucagon in tumor was 20,000. It migrated faster than true glucagon after polyacrylamide gel electrophoresis. No clinical symptoms of glucagonoma developed.
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PMID:Large glucagon-like immunoreactivity in a primary ovarian carcinoid. 396 86

The Escherichia coli outer-membrane endoprotease OmpT mainly cleaves peptide bonds between consecutive basic amino acids. The effect of adjacent residues on cleavage efficiency is currently unknown, except at positions P2 and P2'. Therefore we investigated the effects of amino acid residues upstream of the cleavage site on the ability of OmpT to cleave efficiently a fusion protein carrying human glucagon-like peptide-1 (7-37) in 4 M urea. The P1-P10 residues were replaced by Ala and each substrate was subjected to OmpT digestion. The replacement of Arg residue at P1 blocked the cleavage due to the loss of the cleavage site, and the replacement of Arg residue at P4 maximally reduced the cleavage rate. Conversely, cleavage efficiency increased on replacing Glu at P6. Substitution of the residues at P4 and P6 with several different amino acids showed that OmpT preferred basic residues at these positions, whereas acidic residues had a negative effect. This was also shown to be true with synthetic decapeptide substrates in the absence of urea. The k(cat)/ K(m) ratio increased with basic residues at P4 or P6, mainly due to a lower K(m) rather than an increase in k(cat). On the basis of these findings, we prepared a fusion protein carrying human atrial natriuretic peptide (ANP), a drug for acute congestive heart failure. OmpT released mature ANP from the E. coli-expressed fusion protein. As expected, the introduction of an Arg residue at P4 and P6 enhanced the release of ANP.
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PMID:An analysis of target preferences of Escherichia coli outer-membrane endoprotease OmpT for use in therapeutic peptide production: efficient cleavage of substrates with basic amino acids at the P4 and P6 positions. 1224 47

Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin/glucagon/vasoactive intestinal peptide family, exerts various effects on neuronal development as mediated by the differential expression of PAC1 receptor (PAC1-R) isoforms. The expression changes of PAC1-R isoforms (Hip, Hop1) reported in correlation with retinal development suggest an isoform switch during the second postnatal week. Our aim is to determine the exact period of the isoform shift and to describe the PAC1-R-immunoreactive structures appearing from postnatal day 5 (P5) to P10 in the rat retina. The ratio of Hip and Hop1 receptors was assessed and changes in their expression were followed by Taqman and SybrGreen-based quantitative polymerase chain reaction. For the detection of PAC1-R-expressing retinal structures, anti-PAC1-R, anti-calbindin, anti-protein kinase C, anti-glutamine synthetase, anti-HPC1 and anti-Brn3a antibodies were utilized. At the transcript level, a marked decrease to an undetectable level was measured in Hip mRNA expression from P6 to P9. Hop1 expression appeared to be unchanged from P6 to P9, followed by a significant elevation at P10. A Hip/Hop1 isoform shift occurred between P6 and P7. Immunostaining showed strong PAC1-R labeling from P5 to P10 in ganglion, amacrine, horizontal and rod bipolar neurons and in glial Muller cell processes. The Hop1 isoform was predominantly expressed in various types of retinal cell beginning at P7, because of a dramatic reduction in Hip mRNA level. As the Hop1 receptor is coupled to different signaling cascades, this isoform shift might alter the physiological role of PACAP during this particular period.
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PMID:PAC1-expressing structures of neural retina alter their PAC1 isoform splicing during postnatal development. 2435 4