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)

1. The primordial GRF may have arisen quite early in evolutionary history, at or prior to (i.e. should immunoreactivity data be confirmed in invertebrates) the appearance of jawed vertebrates (Gnathostomates). A common evolutionary pathway using gene duplication may have been utilized to generate the GRF super-family of peptides. As most members of this peptide superfamily are produced in the gastrointestinal tract, the question is posed whether the GRF may have similar origins. 2. It is suggested that the GRF superfamily has two major branches: a) GRF; PRP/PACAP; VIP/PHI; secretin and b) Glucagon/GLP-1/GLP-2. GIP is likely to be a member of the glucagon branch. The two branches may be attributable to gene duplication encoding an ancestral molecule. These gene duplications are likely to have occurred prior to the evolution of vertebrates (conservatively 400-500 million years ago, and possibly 1 billion years ago). It is probable that peptides homologous to GRF, VIP and glucagon will be isolated from invertebrates. These invertebrate sequences will shed further light upon the evolution of this peptide superfamily. 3. Throughout the GRF superfamily, amphiphilic alpha-helical secondary structures represent preferred bioactive conformations. It is assumed that stable, ordered secondary structures conferring enhanced ligand-receptor interactions were conserved due to selective pressures. 4. It is well documented that hypothalamic GRF stimulates adenohypophyseal GH secretion in a variety of species. Thus far, the physiological effects of GRF have been attributed thus to the elevation of GH, and possibly also IGF-I. Recent data suggests a more liberal view; that GRF may also have direct actions in fetal/placental development, reproduction and immune function. Furthermore these direct effects may be mediated via GRF from either hypothalamic or extrahypothalamic (e.g. placenta, testes, ovary, leukocyte) sources. In conclusion, a great wealth of information has accumulated since the discovery of GRF. Examination of the GRF peptide superfamily from an evolutionary perspective has revealed new insights into the synthesis, processing, degradation, conformation and activities of these molecules. Knowledge obtained from these evolutionary comparisons has also become particularly useful in contemporary peptide drug design, which may be liberally viewed as a form of 'artificial evolution' (i.e. the selective pressure being clinical/veterinary requirements for more potent, long-acting GRF analogs).
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PMID:Evolution of the growth hormone-releasing factor (GRF) family of peptides. 129 Sep 54

Vasoactive intestinal peptide (VIP) stimulated cyclic AMP production in rat peritoneal macrophages. The stimulatory effect of VIP was dependent on time, temperature and cell concentration, and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). At 15 degrees C, the response occurred in the 0.1-1000 nM range of VIP concentrations. Half maximal stimulation of cellular cyclic AMP (ED50) was obtained at 1.2 +/- 0.5 nM VIP, and maximal stimulation (about 3-fold basal level) was obtained between 100-1000 nM. The cyclic AMP system of rat peritoneal macrophages showed a high specificity for VIP. The order of potency observed in inducing cyclic AMP production was VIP greater than rGRF greater than hGRF greater than PHI greater than secretin. Glucagon, insulin, pancreastatin and octapeptide of cholecystokinin did not modify cyclic AMP levels at concentrations as high as 1 microM. The beta-adrenergic agonist isoproterenol increased the cyclic AMP production and show additive effect with VIP. Somatostatin inhibits the accumulation of cyclic AMP in the presence of both vasoactive intestinal peptide and isoproterenol. The finding of a VIP-stimulated cyclic AMP system in rat peritoneal macrophages, together with the previous characterization of high-affinity receptors for VIP in the same cell preparation, strongly suggest that VIP may be involved in the regulation of macrophage function.
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PMID:Stimulatory effect of vasoactive intestinal peptide (VIP) on cyclic AMP production in rat peritoneal macrophages. 137 99

The endocrine cells of rainbow trout pyloric ceca and intestine have been investigated immunocytochemically using the avidin-biotin method. Twenty-six antisera were tested and 13 endocrine cell types immunoreacted with antisera to serotonin, somatostatin-25, bombesin, C-flanking bombesin, substance P, salmon PP, NPY, PYY, PP, glucagon, GLP1, Met-enkephalin, and CCK/G. Glucagon and GLP1 immunoreactivities appear in the same cells. Nerves positive to serotonin, substance P, PHI, and VIP were also found. The presence of cells positive to somatostatin-25, C-flanking bombesin, and salmon PP are described for the first time in fish intestine.
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PMID:Endocrine cells and nerves in the pyloric ceca and the intestine of Oncorhynchus mykiss (Teleostei): an immunocytochemical study. 138 78

Previous studies have demonstrated that glucagon-superfamily peptides stimulate insulin release from the pancreatic islets in a glucose dependent manner. In this study we have carried out a structure-activity study of their insulinotropic activity using a rat pancreas perfusion with 5.5 mM glucose concentration. The following peptides were examined: glucagon-like peptide-1(7-36)amide (tGLP-1), glucagon, gastric inhibitory peptide (GIP), peptide having an amino-terminal histidine and carboxy-terminal isoleucine amide (PHI), vasoactive intestinal polypeptide (VIP), growth hormone releasing factor(1-29)amide (GRF), GRF(1-27)amide and synthetic hybrid-peptides of PHI-GRF, PHI(1-11)-GRF(12-27) and PHI(1-20)-GRF(21-27). Their potencies were evaluated as: tGLP-1 = GIP > glucagon > PHI = VIP > PHI(1-20)-GRF(21-27) > PHI(1-11)-GRF(12-27) >> GRF(1-29) = GRF(1-27). It is clear that 0.1 nM tGLP-1 stimulated insulin release, whereas 1 microM GRF(1-29) did not. These results indicate that 1) in addition to N-terminal amino acid (histidine or tyrosine), position 4 (glycine), position 9 (aspartic acid) and position 11 (serine) in the amino acid sequence are important for their insulinotropic activity, 2) not only the N-terminal portion but also the C-terminal portion of these peptides contribute to their insulinotropic activity.
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PMID:Comparison of the insulinotropic activity of glucagon-superfamily peptides in rat pancreas perfusion. 146 9

Vasoactive intestinal polypeptide (VIP) is a neuropeptide, which also modulates some immune functions. Natural killer (NK) cell activity was already found to be diminished by VIP. In the present paper we report that VIP is able to decrease NK cell activity of human large granular lymphocytes (LGL), showing maximal inhibition at doses ranging from 10(-8) to 10(-6) M. Some neuropeptides, belonging to the VIP family (secretin, glucagon, peptide histidine isoleucine, PHI and human growth hormone releasing factor, GHRF), were also tested. Among these peptides, secretin and PHI were shown to be uneffective on NK cell activity whereas glucagon and GHRF were inhibitory. The D50 of GHRF was similar to that of VIP (10(-9) M), the D50 of glucagon was 10(-8) M. A recently synthesized VIP-antagonist (4Cl-D-Phe6-Leu17) was then used to assess its ability to reverse the VIP-mediated inhibition of NK activity. The antagonist was able to completely reverse the inhibitory effect of VIP on NK activity. The VIP-antagonist was also able to reverse the inhibitory effect of glucagon and GHRF, even though to a lesser extent than for VIP. Our data provide a new physiological observation regarding the functional activity of LGL, supporting the presence of a receptor for VIP on human LGL with NK activity.
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PMID:Modulation of human natural killer activity by vasoactive intestinal peptide (VIP) family. VIP, glucagon and GHRF specifically inhibit NK activity. 157 3

Functional vasoactive intestinal peptide (VIP) receptors have been characterized in rat peritoneal macrophages. The binding depended on time, temperature and pH, and was reversible, saturable and specific. Scatchard analysis of binding data suggested the presence of two classes of binding sites: a class with high affinity (kd = 1.1 +/- 0.1 nM) and low capacity (11.1 +/- 1.5 fmol/10(6) cells), and a class with low affinity (kd = 71.6 +/- 10.2 nM) and high capacity (419.0 +/- 80.0 fmol/10(6) cells). Structural requirements of these receptors were studied with peptides structurally or not structurally related to VIP. Several peptides inhibited 125I-VIP binding to rat peritoneal macrophages with the following order of potency: VIP greater than rGRF greater than hGRF greater than PHI greater than secretin. Glucagon, insulin, somatostatin, pancreastatin and octapeptide of cholecystokinin (CCK 26-33) were ineffective. VIP induced an increase of cyclic AMP production. Half-maximal stimulation (ED50) was observed at 1.2 +/- 0.5 nM VIP, and maximal stimulation (3-fold above basal levels) was obtained between 0.1-1 microM. Properties of these binding sites strongly support the concept that VIP could behave as regulatory peptide on the macrophage function.
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PMID:Characterization of functional receptors for vasoactive intestinal peptide (VIP) in rat peritoneal macrophages. 165 77

Vasoactive intestinal polypeptide (VIP) receptors were characterized on non-small cell lung cancer (NSCLC) cells. 125I-VIP bound specifically to membranes derived from 6 NSCLC cell lines. Specific 125I-VIP was time dependent and a linear function of EPLC-65H membrane concentration. 125I-VIP bound with high (Kd = 0.2 nM) and moderate (Kd = 39 nM) affinity to two classes of sites. Pharmacology studies indicated that the order of peptide potency was VIP greater than rGHRH greater than PHI = helodermin greater than secretin greater than glucagon. Also VIP elevated the cAMP levels 10-fold using cell line ADLC-5M2. These data indicate that functional VIP receptors are present on NSCLC cells.
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PMID:Vasoactive intestinal polypeptide binds with high affinity to non-small cell lung cancer cells and elevates cyclic AMP levels. 196 32

Secretin is a 27-amino acid gastrointestinal hormone that stimulates the secretion of bicarbonate-rich pancreatic fluid. We isolated and analyzed the coding region of the gene for the rat secretin precursor. The entire coding region spans 692 base pairs and is divided into four regions corresponding to the signal peptide and NH2-terminal peptide, the secretin peptide and processing signal sequences, a part of the COOH-terminal peptide, and the remainder of the COOH-terminal peptide, which are interrupted by three short introns (81, 105, and 104 base pairs). The organization is similar to those of the genes for other members of the secretin family, glucagon and VIP/PHI-27 precursors, supporting the assumption that the genes for the secretin family peptide precursors originated from a common ancestral gene. We also demonstrated that the secretin precursor gene is widely expressed in the brain and in the hypophysis. The regional expression pattern of the secretin precursor gene in the brain is quite different from those of the glucagon and VIP/PHI-27 precursor genes. The secretin precursor gene is highly expressed in the medulla oblongata and pons of the brain and the hypophysis, the expression levels of which are comparable to those in the duodenum. The secretin precursor mRNA in the brain and the hypophysis has the same coding sequence as that in the duodenum, indicating that secretin in the brain and the hypophysis is produced from the same secretin precursor protein as that in the duodenum. This is the first evidence to be reported that the secretin precursor gene is definitely expressed in the brain.
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PMID:The secretin precursor gene. Structure of the coding region and expression in the brain. 206 29

Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated [Tyr(125I)10]VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function.
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PMID:Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: localization of binding to lactotropes. 215 75

Specific 125I-labelled vasoactive intestinal peptide (VIP) binding was determined in feline renal cortical and medullary plasma membranes. For the cortex, Scatchard analysis of the data resulted in a curvilinear plot with a high-affinity site K0.5 of 8.4 +/- 2.6 nmol l-1 (SE, n = 6) and a second low-affinity site K0.5 204 +/- 16 nmol l-1 with binding site concentrations (Bmax) of 385 +/- 44.5 and 2710 +/- 181.3 fmol mg protein-1 respectively. Conversely a similar analysis of the results obtained for outer medullary membranes gave a single site with a K0.5 of 1.2 +/- 0.2 nmol l-1 (SE, n = 4) and Bmax of 157.8 +/- 24.7 fmol mg-1. Inner medullary membrane binding data. Gave a single site of lower affinity (K0.5 = 62.5 +/- 21.6 nmol l-1; n = 3). Structurally related peptides, glucagon and secretin, were ineffective (up to 1 mumol l-1) in displacing VIP from specific sites in both cortex and medulla. Porcine PHI 1-27 (a peptide having N-terminal histidine and C-terminal isoleucine) and a VIP antagonist [4-Cl-D-Phe6Leu17]VIP both displaced 125I-VIP from cortical and medullary membrane binding sites with IC50 values of 43.0 nmol l-1 and 1.3 mumol l-1 (cortex) and 132.0 nmol l-1 and 1.5 mumol l-1 (medulla) respectively. The localisation of specific VIP binding sites in feline kidney was investigated further by in vitro autoradiography.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localisation and characterisation of functional vasoactive intestinal peptide receptors in feline kidney. 216 36


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