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)

A receptor capable of recognizing VIP-related peptides with unusual functional characteristics and selectivity profile was characterized on human IGR37 melanoma cells. When using either [125I]VIP or [125I]N-AcPACAP27 as a tracer, PACAP38 had the highest affinity, while PACAP27, VIP, helodermin, GRF and the VIP fragment VIP10-28 showed the same low affinity. Moreover, this receptor did not recognize PHM, PHV, helospectin, secretin, GIP, glucagon and glucagon-like peptide-1(7-36). Surprisingly, none of the peptides significantly stimulated the cAMP production. By covalent crosslinking, the receptor was shown to have a M(r) = 60,500.
 ...
PMID:A receptor for VIP-related peptides with an unusual selectivity profile on the melanoma cell line IGR37. 770 17

In order to verify the true GH-releasing effect of glucagon and to explain the mechanism underlying this effect, we studied the effect of glucagon (GLU, 1 mg) administered either iv or im on both basal and GHRH (1 microgram/kg)-induced GH rise in 48 normal short children and adolescents. Moreover, the in vitro effect of GLU on rat anterior pituitary cells was studied. Intravenous administration of GLU induced no significant GH rise. On the other hand, im GLU administration induced a clear-cut GH increase (mean +/- SE GH peak after GLU vs placebo = 25.7 +/- 3.9 vs 10.1 +/- 3.6 micrograms/L, p < 0.01). Intravenous administration of GLU failed to modify the GHRH-induced GH rise either when coadministered with the neurohormone (35.2 +/- 4.1 vs 34.1 +/- 6.0 micrograms/L) or when given 60 min earlier (20.2 +/- 5.8 vs 21.1 +/- 8.3 micrograms/L). Differently from iv GLU, im GLU strikingly potentiated the GH response to GHRH given 90 min later (57.5 +/- 6.3 vs 24.7 +/- 9.1 micrograms/L, p < 0.01). Mean plasma glucose levels increased 30 min after GLU, administered either iv or im, and returned to basal levels 60 min later. GH secretion from dispersed rat pituitary cells was unaffected by incubation with GLU (10(-10)-10(-4) mol/L). Incubation of the cells with 10(-7) mol/L GHRH induced instead a clear-cut stimulation of GH release. In conclusion, our data demonstrate that glucagon per se has not GH-releasing activity as indicated by its uneffectiveness to release GH in vitro and after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucagon stimulates GH secretion after intramuscular but not intravenous administration. Evidence against the assumption that glucagon per se has a GH-releasing activity. 759 31

Calcium and phosphorus metabolism is mainly regulated by PTH through its actions on kidney and bone. PTHrP, which is associated with the hypercalcemia of malignancy syndrome, binds to and activates the same receptor that PTH does. cDNA clones of PTH/PTHrP receptors from rat osteosarcoma (ROS 17/2.8) and opossum kidney (OK) cells are highly homologous and are members of a novel G protein-linked receptor family that includes calcitonin, glucagon, GLP-1, GHRH, VIP, and secretin receptors. Analysis of the protein sequence predicts a receptor with 7 transmembrane domains, a 155 amino acids (aa) extracellular (EC) N-terminal, and 130aa intracellular C-terminal domaina. The extracellular domain has 6 conserved cysteines and 4 potential glycosylation sites. When transfected in COS cells, both receptors are able to bind PTH and PTHrP active fragments with equal affinity. Likewise, agonists activate both adenylate cyclase and phospholipase C efficiently. The N-terminal EC domain and the first EC loop seem to determine the receptor binding capacity with the agonists. Activation of adenylate cyclase and phospholipase C might involve multiple sites between the 3rd helix and the C-terminal tail. Partial characterization of the rat PTH/PTHrP receptor gene demonstrates the existence of at least 15 exons. The first six transmembrane domains are encoded by separated exons. The PTH/PTHrP receptor mRNA is expressed mainly in kidney and bone, and also is widely expressed in many tissues, but not all. A major 2.3-2.5 kb transcript is observed in all these tissues. Nevertheless, 2 larger transcripts are observed in kidney and liver, and multiple smaller mRNA species are observed in kidney, skin, and testis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Mode of action of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in target organs]. 785 77

The effect of intravenous infusion of acetate, propionate and butyrate (0, 3, 10, 30 mumol kg-1 min-1 over 40 min) on the secretion of growth hormone (GH), insulin and glucagon in response to growth hormone-releasing factor (GRF) injection (0.25 micrograms/kg, 10 min after the onset of acid infusion) was determined in six sheep. The intravenous injection of GRF caused a marked increase in plasma GH at every dose of each acid. The GH response to GRF was unaffected by an intravenous infusion of acetate. The basal plasma levels of insulin, glucagon and glucose were unchanged by acetate infusion. The infusion of propionate markedly suppressed the GH response to GRF in a dose-dependent manner. Propionate produced increases in plasma insulin, glucagon and glucose concentrations. Butyrate infusion also caused a significant attenuation of GRF-induced GH secretion. Butyrate infusion stimulated the secretion of both insulin and glucagon and caused hyperglycemia. After cessation of the infusion of propionate or butyrate plasma GH tended to increase again. Plasma somatostatin concentrations, which were measured only for the highest dose of butyrate, were unchanged during acid infusion, but increased on discontinuing the infusion. It is concluded that propionate and butyrate suppress GH secretion, while stimulating the secretion of insulin and glucagon in sheep.
 ...
PMID:Inhibitory effect of volatile fatty acids on GRF-induced GH secretion in sheep. 795 18

In order to facilitate structure-function studies of the glucagon receptor by site-directed mutagenesis, we have designed and synthesized a gene for the rat glucagon receptor. The gene codes for the native 485-amino-acid protein but contains 91 unique restriction sites. To characterize gene expression, a highly specific, high affinity antipeptide antibody was prepared against the receptor. The synthetic gene was expressed in transiently transfected monkey kidney (COS-1) cells. COS cells expressing the synthetic receptor gene bound glucagon with affinity and specificity similar to that of hepatocytes containing native receptor. The transfected COS cells also showed increased intracellular cAMP levels in response to glucagon. The functional role of an aspartic acid residue in the NH2-terminal tail of the receptor was tested by site-directed mutagenesis. This site in the related growth hormone releasing factor receptor was shown to be responsible for the little mouse (lit) genetic defect that results in mice of small size with hypoplastic pituitary glands. Mutant glucagon receptors with amino acid replacements of Asp64 were expressed at normal levels in COS cells but failed to bind glucagon. These results indicate that amino acid Asp64 may play a key role in glucagon binding to receptor.
 ...
PMID:Synthesis and expression of a gene for the rat glucagon receptor. Replacement of an aspartic acid in the extracellular domain prevents glucagon binding. 796 3

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

Secretin is thought to cause choleresis by acting on a receptor expressed by bile duct epithelial cells. In this study, the receptor was characterized using a new preparation of intrahepatic bile duct plasma membranes. Hyperplastic biliary trees were obtained from 3-week bile duct-ligated rats. The biliary trees were homogenized, filtered, and subjected to an aqueous two-phase partition technique to yield highly purified plasma membranes (confirmed by a 14-fold enrichment in gamma-glutamyl transpeptidase activity and a 10-fold enrichment in 125I-secretin binding). 125I-secretin bound saturably with high affinity and in a dose-dependent fashion (Kd = 1.3 +/- 0.1 nM, Bmax = 273 +/- 23 fmole/mg) to purified plasma membranes. The binding characteristics of secretin were most consistent with a single site receptor model. Competitive binding studies indicated that the secretin-related peptides glucagon, peptide histidine isoleucine, gastric inhibitory peptide, and growth hormone releasing factor did not inhibit binding. Vasoactive intestinal peptide (1 microM) reduced maximal binding by 19 +/- 1%. The GTP analogs guanylylimidodiphosphate and guanosine 5'-O-[3-thiotriphosphate] (1 microM) inhibited binding by 16 +/- 2 and 13 +/- 1%, respectively. In conclusion, secretin binds to a specific, high-affinity receptor in intrahepatic bile duct epithelium that is coupled to a G-protein-linked signal transduction system.
 ...
PMID:Secretin receptors in a new preparation of plasma membranes from intrahepatic biliary epithelium. 809 2

The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are encouraging, further progress will require the development of standardized experimental models and a more rigorous approach to experimental design. Many of the studies reported here suffered from small patient numbers, a narrow or nonexistent range of doses, or the use of only one or two dosing regimens. Lack of objective criteria for determining the level of response, e.g., in studies of mental illness or degenerative diseases, and the ethical problems of withholding treatment from some patients to establish proper controls further hamper research in this area. If the questions of efficacy and safety are to be resolved, thorough, well-planned trials will be required.
 ...
PMID:Therapeutic uses of gastrointestinal peptides. 812 75

To examine the structure-activity relationships in the insulinotropic activity of glucagon-like peptide-1(7-36) amide (GLP-1(7-36)amide), we synthesized 16 analogues, including eight which were designed by amino acid substitutions at positions 10 (Alal0), 15 (Serl5), 16 (Try16), 17 (Arg17), 18 (Lys18), 21 (Gly21), 27 (Lys27) and 31 (Asp31) of GLP-1(7-36)amide with an amino acid of GH-releasing factor possessing only slight insulinotropic activity, and three tentative antagonists including [Glu15]-GLP-1(8-36)amide. Their insulinotropic activities were assessed by rat pancreas perfusion experiments, and binding affinity to GLP-1 receptors and stimulation of cyclic AMP (cAMP) production were evaluated using cultured RINm5F cells. Insulinotropic activity was estimated as GLP-1(7-36)amide = Tyr16 > Lys18, Lys27 > Gly21 > Asp31 >> Ser15, Arg17 > Ala10 >> GRF > [Glu15]-GLP-1(8-36) amide. Displacement activity against 125I-labelled GLP-1(7-36)amide binding and stimulatory activity for cAMP production in RINm5F cells correlated well with their insulinotropic activity in perfused rat pancreases. These results demonstrate that (1) positions 10 (glycine), 15 (aspartic acid) and 17 (serine) in the amino acid sequence of GLP-1(7-36)amide, in addition to the N-terminal histidine, are essential for its insulinotropic activity through its binding to the receptor, (2) the amino acid sequences for the C-terminal half of GLP-1(7-36)amide also contribute to its binding to the receptor, although they are less important compared with those of the N-terminal half, and (3) [Glu15]-GLP-1(8-36)amide is not an antagonist of GLP-1(7-36)amide as opposed to des-His1 [Glu9]-glucagon amide which is a potent glucagon antagonist.
 ...
PMID:Structure-activity relationships of glucagon-like peptide-1(7-36)amide: insulinotropic activities in perfused rat pancreases, and receptor binding and cyclic AMP production in RINm5F cells. 813 51

Ion-spray ionization mass spectrometry with gentle conditions for solvent removal has been reported as a useful tool for detection of high-affinity noncovalent complexes of biological relevance formed in solution. Two main objectives of this study were (i) to find whether other types of electrospray ionization (ESI) sources, e.g. where the solvent is removed with the help of heat (thermally assisted electrospray), could be utilized for detection of noncovalent biological complexes of high and low affinity and (ii) to find whether ESI-MS can be used for detection of the association of bovine serum albumin (BSA) with biologically active peptides. Using a well-defined high-affinity association of FK506 with its binding protein (FKBP) as model system we proved that ESI-MS with thermally assisted interphase can be used for detection of the FK506-FKBP complexes in a similar way as was previously shown for electrospray mass spectrometry (Ganem et al., J. Am. Chem. Soc. 113, 6294 (1991)). In mixtures of BSA with a 9-10 molar excess of biologically active peptides, such as growth hormone releasing factor (GRF), glucagon, bradykinin or insulin in ammonium acetate at pH 7.5, complexes with a ratio of 1:1, 1:2 and in some cases 1:3 were detected. On the other hand, these complexes disappeared upon acidification, pointing to their noncovalent nature.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Application of thermally assisted electrospray ionization mass spectrometry for detection of noncovalent complexes of bovine serum albumin with growth hormone releasing factor and other biologically active peptides. 816 73


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