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

Specific binding sites for 125I-labelled rat peptide-histidine-isoleucine (PHI) were identified on rat insulinoma-derived RINm5F cells. The concentrations of peptides producing half-maximal displacement of label were rat PHI, 0.36 +/- 0.14 nM, vasoactive intestinal polypeptide (VIP), 0.38 +/- 0.13 nM and secretin, approximately 0.2 microM. Glucagon and glucagon-like peptide-1(7-36)amide were without effect on binding. PHI and VIP produced dose-dependent increases in cAMP production in the cells that were significantly (P less than 0.05) above unstimulated rates for ligand concentrations between 10(-8) and 10(-6) M. Both PHI and VIP produced a small but significant (P less than 0.05) enhancement in the rate of release of immunoreactive insulin from the cells but the effect was not dose dependent.
 ...
PMID:Binding sites for peptide-histidine-isoleucine (PHI) on rat insulinoma-derived RINm5F cells. 285 Sep 58

The hypothalamic peptide vasoactive intestinal peptide (VIP) stimulates ACTH and endorphin secretion by the AtT20/D16 clonal strain of mouse pituitary tumor cells. The dose dependence for VIP stimulation of hormone release is biphasic, indicating that VIP is able to activate at least two classes of receptors in D16 cells (ED50 = 1.6 and 160 nM). We show that at high concentrations (ED50 greater than or equal to 150 nM), other natural peptides with primary structures homologous to that of VIP also increased ACTH secretion by D16 cells, whereas structurally unrelated peptides did not. The stimulatory actions of GH-releasing factor (GRF) and porcine heptacosapeptide with amino-terminal histidine and carboxy-terminal isoleucine amide (PHI) were mediated by high affinity VIP receptors because their effects were not additive with that of 10 nM VIP. In addition, GRF and PHI behaved as antagonists at low affinity VIP receptors; both peptides inhibited stimulation by 1 microM VIP. In contrast, glucagon and gastric inhibitory polypeptide appeared to stimulate ACTH release via low affinity VIP receptors because their effects were additive with that of 10 nM, but not 1 microM, VIP. Since all of the VIP-like peptides increased ACTH secretion only at high concentrations, they were unlikely to represent a physiological ligand for the receptor activated by high concentrations of VIP. Therefore, we determined whether cross-reactivity occurred between VIP-like peptides and corticotropin-releasing factor (CRF), a potent stimulator of ACTH secretion both in vitro and in vivo. The dose-response curve for CRF stimulation of ACTH secretion by D16 cells extended over more than a 1000-fold range of concentrations and was biphasic (ED50 = 2.6 and greater than 300 nM), indicating that CRF interacted with multiple receptor types in D16 cells. However, since the effect of 10 nM CRF was additive with that of 1 microM VIP, the CRF receptor was not the site at which high concentrations of VIP stimulated ACTH release. In contrast, the effect of 1 microM CRF was not additive with that of 1 microM VIP or other VIP-like peptides. Therefore, high concentrations of CRF and the previously recognized VIP-like peptides stimulated ACTH secretion by overlapping pathways. Comparison of the amino acid sequence of CRF with those of the VIP-like peptides showed that 18 of the 41 amino acids in CRF match a corresponding amino acid in at least 1 member of the VIP peptide family.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Peptide specificity for stimulation of corticotropin secretion: activation of overlapping pathways by the vasoactive intestinal peptide family and corticotropin-releasing factor. 285 86

Preganglionic nerve stimulation leads to an acute elevation of tyrosine hydroxylase (TH) activity in the rat superior cervical ganglion. This effect is mediated in part by acetylcholine, acting via nicotinic receptors, and in part by a noncholinergic neurotransmitter. As a first step in an attempt to identify this noncholinergic transmitter, we have examined a number of biogenic amines, purine nucleotides, neuropeptides, and other compounds for their ability to increase TH activity. Secretin, vasoactive intestinal peptide (VIP), and PHI (a 27-amino acid peptide with an NH2-terminal histidine and a COOH-terminal isoleucine amide), all members of the secretin family of peptides, increased TH activity acutely. Human pancreatic growth hormone-releasing factor, glucagon, and gastric inhibitory peptide (three other members of this peptide family) and all other transmitter candidates tested had no effect on this enzyme activity. We have examined the possibility that this peptidergic regulation of TH activity is mediated via changes in adenosine 3',5'-cyclic monophosphate (cAMP) levels. When the six members of the secretin family were tested for their ability to increase cAMP levels in the ganglion, secretin, VIP, and PHI significantly increased this cyclic nucleotide, whereas growth hormone-releasing factor, glucagon, and gastric inhibitory peptide produced no significant effects. The rank orders of potency and of efficacy of secretin, VIP, and PHI in altering TH activity and cAMP levels were identical. Furthermore, a strong correlation was found between the cAMP level and the TH activity in individual ganglia exposed to these peptides. Finally, 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin also increased TH activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of the concentration of adenosine 3',5'-cyclic monophosphate and the activity of tyrosine hydroxylase in the rat superior cervical ganglion by three neuropeptides of the secretin family. 286 28

In our effort to identify the proteolytic specificity of various hemorrhagic toxins isolated from western diamondback rattlesnake venom, hemorrhagic toxin b was isolated in homogeneous form by previously published methods. Hemorrhagic toxin b hydrolyzed glucagon, producing six fragments. The proteolytic sites were identified as Thr(5)-Phe(6), Thr(10)-Ser(11), Asp(15)-Ser(16), Asp(21)-Phe(22) and Try(25)-Leu(26). When oxidized insulin B chain was used, proteolysis occurred at four sites: Asn(3)-Gln(4), His(10)-Leu(11), Tyr(16)-Leu(17) and Gly(23)-Phe(24). The proteolytic specificity of hemorrhagic toxin b is quite different from those of the nonvenom proteases such as thermomycolin, aspergillopeptidase c, alkaline protease from Aspergillus flavus, elastase, subtilisin and papain.
 ...
PMID:Proteolytic specificity of hemorrhagic toxin b from Crotalus atrox (western diamondback rattlesnake) venom. 286 65

Cyclic hexapeptide analogs of somatostatin with insulin, glucagon, and growth hormone (GH) release inhibitory potencies of 50-200 times those of somatostatin have been synthesized. Replacement of the Phe-7 residue with histidine has resulted in increased oral bioavailability and duration of action. Metabolic degradation of L-Trp containing analogs upon oral administration has also been overcome by incorporation of histidine. The all L-amino acid containing analog cyclo(NMePhe-His-Trp-Lys-Val-Ala) shows oral bioavailability comparable to D-Trp containing analogs.
 ...
PMID:Somatostatin analogs with improved oral bioavailability. 288 53

Neonatal mice, under fasting conditions, are susceptible to the development of lesions in the arcuate nucleus (AN) of the hypothalamus, with high doses of monosodium L-glutamate (MSG). Feeding of nutrients (e.g., sugars and L-amino acids) has been shown to have a protective effect against the development of these lesions. The purpose of these studies was to elucidate the mechanism of this protective effect. Histopathologic examination of lesions of the AN demonstrated that feeding of weaning mice before subcutaneous administration of toxic doses of MSG suppressed the development of these lesions, as compared to fasted controls. Similarly, the number of necrotic cells in the AN of neonates administered toxic doses of MSG subcutaneously was reduced when D-glucose and L-arginine were administered orally. Atropine obliterated the protective effect of D-glucose. Pretreatments consisting of gastric inhibitory polypeptide (GIP) + oral D-glucose had a protective effect of higher potency than GIP alone. Pretreatments with insulin, anorexigenic peptide (pyroGlu-His-Gly), cholecystokinin, glucagon, bombesin, and substance P (in decreasing order of effectiveness) demonstrated a protective effect against the AN lesion in neonates, whereas somatostatin and beta-endorphin had no effect. Results suggest that the protective effect of nutrients may in part be due to the stimulation of peptide hormone release during the postabsorptive phase. It is postulated that the effect of entero-pancreatic hormone, especially insulin, is to enhance the tolerance of AN neurons of neonatal mice to the toxic dose of L-glutamate.
 ...
PMID:Mealing and related hormone release suppress hypothalamic lesions of neonatal mice by L-glutamate. 288 96

The human colon adenocarcinoma cell line HT-29 in culture exhibits a cyclic AMP production system highly sensitive to vasoactive intestinal peptide (VIP), making HT-29 cells a unique cultured cell system for studying the mechanism of VIP action [Laburthe, Rousset, Boissard, Chevalier, Zweibaum & Rosselin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2772-2775]. The quantitative characteristics of VIP receptors in HT-29 cells and their structural requirement and molecular size were studied. 125I-labeled VIP bound in a time-dependent manner to HT-29 cell homogenates. At equilibrium (60 min incubation at 30 degrees C), unlabelled VIP in the 0.01-10 nM concentration range competed with 125I-VIP for binding to cell homogenates. Scatchard analysis of binding data gave a straight line, indicating that VIP bound to a single population of sites with a KD of 0.12 +/- 0.02 nM and a capacity of 120 +/- 9 fmol/mg of protein. The structural requirement of these receptors was studied with peptides structurally related to VIP, either natural or synthetic. Several peptides inhibited 125I-VIP binding to HT-29 cell homogenates with the following order of potency, which is typical of the human VIP receptor: VIP (IC50 = 0.1 nM) greater than VIP-(2-28)-peptide (IC50 = 13 nM) greater than human growth hormone releasing factor (IC50 = 56 nM) greater than peptide histidine isoleucine amide (IC50 = 80 nM) greater than secretin (IC50 greater than 10 000 nM). To characterize the molecular component(s) of the VIP receptor in HT-29 cells, 125I-VIP was covalently bound to cell homogenates by using the cross-linker dithiobis(succinimidyl propionate). Sodium dodecyl sulphate/polyacrylamide-gel autoradiographic studies of affinity-labelled cell homogenates revealed two major bands, corresponding to 125I-VIP-protein complexes of Mr 66 000 and 16 000. The labelling of the Mr-66 000 component was specific, since it was abolished by native VIP, whereas that of the Mr-16 000 component was not. Densitometric scanning of autoradiographs indicated that the labelling of the Mr-66 000 complex was inhibited by low VIP concentrations in the 0.1-10 nM range (IC50 = 0.6 nM), but was unaffected by 1 microM-glucagon or octapeptide of cholecystokinin. It was also decreased by VIP-(2-28)-peptide with a potency 1% that of VIP. Assuming that one molecule of 125I-VIP bound per molecule of protein, one protein of Mr 63 000 was identified as a component of the VIP receptor in HT-29 cells.
 ...
PMID:Molecular identification and structural requirement of vasoactive intestinal peptide (VIP) receptors in the human colon adenocarcinoma cell line, HT-29. 299 37

In this study, we determined the ability of four N-terminally modified derivatives of glucagon, [3-Me-His1,Arg12]-, [Phe1,Arg12]-, [D-Ala4,Arg12]-, and [D-Phe4]glucagon, to compete with 125I-glucagon for binding sites specific for glucagon in hepatic plasma membranes and to activate the hepatic adenylate cyclase system, the second step involved in producing many of the physiological effects of glucagon. Relative to the native hormone, [3-Me-His1,Arg12]glucagon binds approximately twofold greater to hepatic plasma membranes but is fivefold less potent in the adenylate cyclase assay. [Phe1,Arg12]glucagon binds threefold weaker and is also approximately fivefold less potent in adenylate cyclase activity. In addition, both analogues are partial agonists with respect to adenylate cyclase. These results support the critical role of the N-terminal histidine residue in eliciting maximal transduction of the hormonal message. [D-Ala4,Arg12]glucagon and [D-Phe4]glucagon, analogues designed to examine the possible importance of a beta-bend conformation in the N-terminal region of glucagon for binding and biological activities, have binding potencies relative to glucagon of 31% and 69%, respectively. [D-Ala4,Arg12]glucagon is a partial agonist in the adenylate cyclase assay system having a fourfold reduction in potency, while the [D-Phe4] derivative is a full agonist essentially equipotent with the native hormone. These results do not necessarily support the role of an N-terminal beta-bend in glucagon receptor recognition. With respect to in vivo glycogenolysis activities, all of the analogues have previously been reported to be full agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Receptor binding and adenylate cyclase activities of glucagon analogues modified in the N-terminal region. 301 Oct 69

The effects of VIP and of peptides of the VIP family: secretin, glucagon, the porcine histidine isoleucine containing peptide (PHI) and the rat hypothalamic growth hormone-releasing hormone (rhGRF) on the cyclic AMP and inositol phosphate contents of isolated rat superior cervical ganglia were investigated. We demonstrate that VIP is able to provoke a large inositol lipid breakdown by acting directly on ganglionic cells. This observation suggests the presence in rat superior cervical ganglia of a new type of receptors for VIP or for an unidentified peptide structurally related to VIP.
 ...
PMID:Vasoactive intestinal polypeptide increases inositol phospholipid breakdown in the rat superior cervical ganglion. 301 40

Crude fresh membranes from rat liver and membranes from rat heart obtained according to Snyder and Drummond were tested for adenylate cyclase activation by glucagon (Gn) and seven glucagon analogs including (Ala2)-, (Arg12)-, (Des-His1, Arg12), (Phe1, Arg12)-, (N-Ac-His1, Arg12)-, (1-Me-His1, Arg12)-, and (3-Me-His1, Arg12)-glucagon. (Des-His1, Arg12)-glucagon acted as a competitive antagonist in heart membranes and as a partial agonist in liver membranes. Results obtained with analogs where His1 was modified suggest that the size of the imidazole ring and the charge of its nitrogen 1, but not the charge of the free amino group of histidine, played a major role in biological activity. When comparing functional glucagon receptors in liver and heart membranes, it appears that the first receptors were more sensitive to the hormone and more efficiently coupled to adenylate cyclase.
 ...
PMID:Comparative efficacy of seven synthetic glucagon analogs, modified in position 1, 2 and/or 12, on liver and heart adenylate cyclase from rat. 301 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>