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)

PHI--a new candidate hormone from porcine intestinal tract-- corresponds to a linear heptacosapeptide amide of remarkable sequence homology to the known members of the glucagon family, particularly to the vasoactive intestinal peptide (VIP) and secretin. The position 24 usually occupied by an aminodicarboxylic acid omega-amide, in the present case, however, carries a glutamic acid, thus opening the question of whether this structural feature is related to desamidation in one of the isolation and characterization steps or of whether it is significant for this peptide factor. Consequently the heptacosapeptide amides corresponding to the proposed primary structure and to its 24-glutamine analogue have been synthesized. Comparative chromatographic and biological studies on the natural and the two synthetic products have confirmed the correctness of the primary structure proposed for the isolated PHI. Since [24-glutamic acid] and [24-glutamine]PHI exhibit no significant differences in their biological potencies, the main question is still open of whether the position 24 in native PHI is occupied by the aminodicarboxylic acid omega-amide (glutamine) or by N-substituted derivatives (N-glycosyl).
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PMID:Synthesis of the porcine intestinal peptide PHI and its 24-glutamine analogue. 668 13

Naturally occurring peptides with biological actions have in most cases been detected by observing their biological activities in crude extracts and their isolation has been followed using bioassays. As a complement to the classical biological detection systems, we have proposed a chemical detection system based on fragmentation of peptides in tissue extracts followed by identification of certain of these peptide fragments having distinct chemical features. One such chemical feature is the C-terminal amide structure which is characteristic of many biologically active peptides. We have devised a chemical assay method for peptides having such a structure and have found several previously unknown peptide amides in procine upper small intestinal tissues. We report here the isolation and characterization of two of them, designated PHI and PYY. PHI is related to secretin, vasoactive intestinal polypeptide (VIP, glucagon and gastric inhibitory polypeptide (GIP); PYY is related to the pancreatic polypeptide and to neurotensin. Both peptides exhibit biological activities and appear to be present not only in the intestine but also in brain.
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PMID:Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. 689 50

Regulatory peptides are likely to have a role in the control of net intestinal fluid transport. PHI is a peptide recently isolated from porcine duodenum which has been shown to have sequence homologies with other peptides of the glucagon-secretin family. We have studied the effect of intravenous infusion of synthetic PHI on net intestinal fluid transport in the rat small intestine. During PHI infection net absorption was reduced in the duodenum and jejunum and net secretion was observed in the ileum. Thus synthetic PHI appears to be capable of strongly stimulating intestinal secretion in the rat.
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PMID:PHI stimulates intestinal fluid secretion. 689 69

A new peptide, designated PHI (PHI-27), has been discovered and isolated from porcine upper intestinal tissue by using a chemical method for finding peptide hormones and other active peptides. The method is based on chemical detection of peptides having the cOOH-terminal alpha-amide structure, which is an unusual chemical feature of some peptide hormones and active peptides. Porcine PHI was found in the intestinal extract by the presence of its COOH-terminal isoleucine amide structure. It consists of 27 amino acid residues and has the following amino acid sequence: His-Ala-Asp-Gly-Val-Phe-Thr-Ser-Asp-Phe-Ser-Arg-Leu-Leu-Gly-Gln-Leu-Ser-Ala-Lys -Lys-Tyr-Leu-Glu-Ser-Leu-Ile-NH2. The remarkable sequence homology of PHI to the vasoactive intestinal peptide, secretin, glucagon, and gastric inhibitory polypeptide indicates that this peptide is a member of the glucagon-secretin family. Several biological activities of PHI, similar to those of vasoactive intestinal peptide and secretin, have been reported.
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PMID:Isolation and characterization of the intestinal peptide porcine PHI (PHI-27), a new member of the glucagon--secretin family. 694 44

Histological, immunocytochemical and immunofluorescence methods were employed to study the oesophagus and stomach of the elephant. The histological findings were in line with the situation in monogastric species like swine and man. In the mucosa of the stomach, endocrine cells were immunoreactive to gastrin, somatostatin, chromogranin A and serotonin. Nerve cells immunoreactive to somatostatin, bombesin, VIP, PHI and CGRP were detected in the submucosal and myenteric plexus of the stomach. In the stomach, the absence of glucagon cells and the presence of endocrine cells immunoreactive to PYY, are in contrast to the situation in mammals and need further investigation. Small gastric ulcers were observed in some of the specimens.
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PMID:The oesophagus and stomach of the African elephant: a histological, immunocytochemical and immunofluorescence study. 759 75

Vasoactive intestinal peptide (VIP) receptors were investigated in rat peritoneal macrophage membranes (RPMM) using [125I]VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. The Scatchard analysis of binding data was consistent with the existence of two classes of VIP binding sites with Kd values of 0.60 +/- 0.08 and 275 +/- 39 nM and binding capacities of 580 +/- 71 and 72,500 +/- 810 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP. These pharmacological studies showed the following order of potency: VIP (IC50 = 1 nM) > rGRF (IC50 = 13 nM) > PHI (IC50 = 421 nM) >> secretin. Glucagon, somatostatin, insulin octapeptide of cholecystokinin [CCK(26-33)], and pancreastatin were ineffective at concentrations up to 1 microM. Binding of [125I]VIP to membranes is markedly reduced by increasing the ionic strength of incubation medium. Treatment of membranes with dithiothreitol, trypsin, and phospholipases A2 and C resulted in a loss of the ability of these membranes to bind VIP. However, treatment with phospholipase D did not affect binding of VIP by membranes. The molecular characterization of VIP receptors in RPMM was performed after [125I]VIP cross-linking to membranes using the cross-linker dithiobis (succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins revealed specific [125I]VIP-protein complexes of M(r) 55,000 +/- 1700, 35,000 +/- 900, and 22,000 +/- 500.
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PMID:Characteristics of receptors for VIP in rat peritoneal macrophage membranes. 800 37

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone and is considered as a new therapeutic tool in the treatment of diabetes mellitus. This study was designed to precisely characterize the binding behavior and activation of the recombinant GLP-I receptor against naturally occurring ligands of the glucagon/VIP/secretin peptide hormone family. CHO-cells were stably transfected with a plasmid containing a cDNA encoding for the rat GLP-I receptor. Northern blot analysis with this cDNA showed a single band of 2.7 kb in CHO cells, while in RINm5F cells, three bands of 2.7, 3.4, and 3.6 kb were specifically labelled. In receptor-binding studies 125I-GLP-I was displaced by GLP-I and weakly by PHI and oxyntomodulin but not by helodermin, helospectin I, helospectin II, secretin, VIP, and PACAP-38. Intracellular cAMP generation was stimulated by GLP-I, PHI, and oxyntomodulin. Helodermin, helospectin I, helospectin II, secretin, VIP, and PACAP-38 were not able to displace 125I-GLP-I from its receptor or to stimulate intracellular cAMP production. This data shows that the GLP-I receptor is characterized by a high ligand specificity.
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PMID:Ligand-specificity of the rat GLP-I receptor recombinantly expressed in Chinese hamster ovary (CHO-) cells. 801 94

The effect of vasoactive intestinal peptide (VIP) on stimulation of adenylyl cyclase in fetal human nonpigmented ciliary epithelial (NPE) and pigmented ciliary epithelial (CPE) cells was studied. 1 microM VIP elicited a 5-10 fold increase in intracellular cAMP in NPE cells from three fetal donors, but caused little or no response in CPE from two fetal donors and other ocular cell types employed as controls. Appearance of cAMP in the extracellular medium was stimulated in NPE but not in CPE in response to VIP. Both NPE and CPE gave similar cAMP responses (8-13 fold) to the beta-adrenergic agonist, isoproterenol. Binding studies of [125I]VIP to intact NPE and CPE revealed that VIP bound to NPE cells at a high affinity site (KD = .33 nM and a low affinity site (KD = 16 nM), whereas VIP bound to CPE cells only at the low affinity site (KD = 18 nM). In NPE cells, VIP stimulated cAMP formation with an EC50 of approximately 0.6-1 nM, similar to the high affinity binding site KD, with maximal stimulation at 10 nM. Four peptides with various degrees of sequence homology to VIP were also studied. Of these, PHM and PHI stimulated cAMP with EC50s of 50 and 300 nM, respectively, while secretin and glucagon stimulated only at concentrations above 0.1 microM. These results suggest that in fetal human ciliary epithelium, as in rabbit ciliary epithelium (Mittag et al., J Pharm Exp Ther 241: 230, [1987]), VIP stimulation of adenylyl cyclase is a characteristic of NPE but not CPE cells.
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PMID:High affinity vasoactive intestinal peptide receptors on fetal human nonpigmented ciliary epithelial cells. 803 89

Receptors for VIP in mouse peritoneal macrophages (MPM) were examined using [125I]labeled VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, pH, temperature and cell concentration. At 15 degrees C, the stoichiometric data suggested the presence of two classes of VIP receptors with Kd values of 1.05 +/- 0.2 and 66.4 +/- 11.0 nM and binding capacities of 19.2 +/- 2.8 and 706.6 +/- 172.0 fmol VIP/10(6) cells. The interaction showed a high degree of specificity, as suggested by competition experiments with various peptides structurally related to VIP as follows: VIP > helodermin > rGRF > PHI >> secretin. Glucagon, pancreastatin, somatostatin, insulin, and octapeptide of cholecystokinin (CCK 26-33) were ineffective at concentrations as high as 1 microM. VIP was a potent and efficient stimulator of cyclic AMP production in MPM. The stimulation was observed at a concentration as low as 0.01 nM VIP. Half-maximal stimulation (ED50) was observed at 1.0 +/- 0.2 nM VIP, and maximal stimulation (three-fold above basal levels) was obtained between 0.1-1 microM. The cyclic AMP system of mouse peritoneal macrophages showed a high specificity for VIP. The order of potency observed in inducing cyclic AMP production was VIP > helodermin > rGRF > PHI >> secretin. Glucagon, insulin, pancreastatin, somatostatin and octapeptide of cholecystokinin did not modify cyclic AMP levels at concentrations as high as 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of VIP receptors in mouse peritoneal macrophages: functional and molecular characterization. 830 Aug 60

The binding of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) to rat lung membranes was investigated using [125I]PACAP-38 as radioligand. Binding was rapid at 37 degrees C, reversible, saturable, and time, concentration, and temperature dependent. Kinetic parameters derived from saturation experiments revealed a Kd = 100 +/- 15 pM, Bmax = 310 +/- 36 fmol/mg protein, and a Hill slope factor (nH) of 1.17 +/- 0.12. Various chemically synthesized analogues of PACAP-38, as well as related peptides, were tested for their ability to displace [125I]PACAP-38. Of those that had an IC50 < 0.2 microM, the following order of potency was determined: PACAP-38 (IC50 = 25 nM) > or = [Ile2]PACAP-38 (IC50 = 31 nM) > PACAP-27 (IC50 = 54 nM) > [Tyr1]PACAP-38 (IC50 = 104 nM) > GHRH(1-29)NH2 (IC50 = 108 nM) > PHI (IC50 = 181 nM) > [Ser2]PACAP(2-38) (IC50 = 198 nM). Glucagon, PHM, secretin, and GIP exhibited little affinity in the same binding assay. Vasoactive intestinal peptide (VIP) had an IC50 in excess of 1 microM. When [125I]VIP was used as radioligand, PACAP-27 had an IC50 = 0.2 nM > PACAP-38 (IC50 = 0.5 nM) > VIP (IC50 = 16 nM). A novel analog of PACAP-38, [4-Cl-D-Phe6,Leu17]PACAP-38, was able to displace [125I]VIP very efficiently (IC50 = 1 nM), but had little potency in displacing [125I]PACAP-38 (IC50 = 320 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) with rat lung membranes. 839 24


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