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 stimulatory effects of neurotensin (NT) and several NT fragments were evaluated in two pharmacological preparations: rat stomach strips and isolated spontaneously beating atria of guinea-pigs.2 In rat stomach strips, NT elicited a dose-dependent contractile effect in concentrations varying between 1.3 x 10(-9) and 5.4 x 10(-7) M.3 The contractile effect of NT (1.3 and 5.4 x 10(-8) M) in this tissue was not modified by atropine (3.4 x 10(-7) M), methysergide (2.0 x 10(-6) M), a mixture of cimetidine (8.0 x 10(-6) M) and diphenhydramine (7.8 x 10(-6) M), indomethacin (1.4 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), glucagon (2.0 x 10(-6) M) or somatostatin (3.0 x 10(-7) M).4 Rat stomach strips desensitized by bradykinin (6.1 x 10(-6) M) or substance P (7.4 x 10(-6) M) maintained their sensitivities to NT (1.3 and 5.4 x 10(-8) M).5 In guinea-pig atria, NT produced a dose-dependent positive inotropic action in concentrations varying between 5.4 x 10(-10) and 2.7 x 10(-7) M.6 The inotropic effect of NT (2.7 x 10(-9) M) was not influenced by methysergide (2.8 x 10(-6) M), atropine (3.4 x 10(-7) M), practolol (1.5 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), or indomethacin (1.4 x 10(-5) M), but it was reduced by 37% by cimetidine (4.0 x 10(-5) and 2.0 x 10(-4) M). A combination of cimetidine (4.0 x 10(-5) M) and diphenhydramine (3.9 x 10(-6) M) did not produce a greater inhibition of NT than cimetidine alone.7 Atria desensitized by bradykinin (6.1 x 10(-6) M) or glucagon (2.0 x 10(-6) M) maintained their sensitivities to NT (2.7 x 10(-9) M). Substance P was inactive both as an agonist or antagonist of NT.8 These results suggest the existence of specific NT receptors in rat stomach strips and guinea-pig atria.9 The data derived from our structure-activity study suggest that the minimum structure required for the full stimulation of NT receptors in these two preparations is H-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)-OH. The sequence PyroGlu(1)-Leu(2)-Tyr(3)-Glu(4)-Asn(5)-Lys(6)-Pro(7)-Arg(8)- and the amino acids Ile(12) and Leu(13) appear to contribute mainly to the affinity or binding of NT to its receptor. The chemical groups responsible for the full activation (intrinsic activity) of NT receptors seem to be located in the sequence -Arg(9)-Pro(10)-Tyr(11).
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PMID:The stimulatory effects of neurotensin and related peptides in rat stomach strips and guinea-pig atria. 735 2

The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was assessed by the expression of collecting duct-specific antigens and the ability of vasopressin to increase by nine-fold cAMP synthesis. Glucagon and adenosine stimulated cAMP synthesis, and atrial natriuretic peptide stimulated cGMP synthesis in a concentration-dependent manner. Bradykinin, adenosine and angiotensin increased intracellular calcium concentration ([Ca2+]i). Because adenosine can regulate tubular functions, we examined its role on glucagon-induced cAMP synthesis. Using adenosine analogs, we demonstrated that HCT cells both expressed adenosine type-2 (A2) receptors which stimulated cAMP production, and adenosine type-1 (A1) receptors linked to [Ca2+]i increase which inhibited glucagon-stimulated cAMP synthesis. The inhibitory effect was abolished by pertussis toxin, and was neither due to [Ca2+]i increase nor to protein kinase C activation, which indicated that some A1 adenosine receptors were directly negatively coupled to adenylyl cyclase. These results suggest that adenosine can modify human cortical collecting duct functions in opposite ways according to the adenosine receptor activated.
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PMID:Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct cell line. 763 60

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)
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PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

Glucagon (Glu) influences renal tubular function and growth, although the signal transduction of Glu in the kidney still remains obscure. Rabbit cortical tubules were transformed by the pSV-neo3 gene to make a homogeneous cell colony, which responded to vasopressin but not to parathyroid hormone. The [Ca2+]i of the cells at the 9-10th passages was measured by the fluorescence indicator, fura-2. The [Ca2+]i was increased by Glu (10(-8) M) or bradykinin (10(-8) M), between which heterologous desensitization was observed. The Glu range of 10(-14) to 10(-6) M) significantly increased [Ca2+]i, while cAMP was not produced at any dose of Glu. Since the ranges of doses were from physiological to pharmacological, two concentrations of 10(-13) and 10(-8) M were employed to investigate the mechanisms. Glu at 10(-13) M led to a sustained rise in [Ca2+]i, which was completely blocked by external EGTA (5 mM, Ca-free solution). Glu at 10(-8) M provided a similar level of peak and sustained rise in [Ca2+]i, the sustained phase of which was blunted in Ca-free solution. Inositol tri/tetra phosphates were significantly increased by 10(-8) M, but not by 10(-13) M Glu. These data suggest that [Ca2+]i elevation is a major component of Glu-induced second messengers in the physiological and pharmacological range of doses of Glu, and that there might be two classes of pathways leading to increase in [Ca2+]i in transformed rabbit cortical collecting tubule cells.
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PMID:Glucagon increases intracellular free calcium in a distal tubular cell line. 802

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)
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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

A dipeptidyl-peptidase IV was purified from the culture medium of the human-pathogenic fungus Aspergillus fumigatus. The enzyme has an apparent molecular mass of 95 kDa and contained approximately 10 kDa of N-linked carbohydrate. This glycoprotein is antigenic and has all characteristics of the class IV dipeptidyl-peptidases: removal of Xaa-Pro and to a lesser extent Xaa-Ala dipeptides from the N termini of peptides, including bioactive peptides such as neuropeptide Y, [des-Arg1] bradykinin, and glucagon-like peptide 1, activity at neutral pH, and presence in the amino acid sequence of the Gly-X-Ser-X-Gly consensus motif of the serine-hydrolases and the putative catalytic triad (Ser613, Asp690, His725) of the dipeptidyl-peptidases. Moreover, the last 200 amino acids displayed 60 to 65% similarity with the other dipeptidyl-peptidases IV from rat, mouse, human, and yeast. However, unlike the other dipeptidyl-peptidases, the dipeptidyl-peptidase IV of A. fumigatus is a secreted enzyme with a cleavable signal peptide. Expression of a recombinant dipeptidyl-peptidase IV of A. fumigatus has been attained in the yeast Pichia pastoris.
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PMID:Dipeptidyl-peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to humans. 923 52

To evaluate the effect of bradykinin (BK) on rat islet alpha, beta, and delta cells, the rat pancreas was perfused in situ with BK (1 mumol/L) for 30 minutes via a cannula placed in the celiac artery. Insulin, glucagon, and somatostatin concentrations in the effluent were measured to determine the effect of BK on the secretion of these hormones. The BK concentration of the rat pancreas was also measured. Basal secretion of insulin, glucagon, and somatostatin in medium containing 6 mmol/L glucose was maintained at 6.5 +/- 0.5 ng/mL 124 +/- 8 pg/mL, and 511 +/- 22 pg/mL (n = 12), respectively. BK (1 mumol/L) induced a transient peak that was 3.7-fold of the baseline concentration within 3 minutes, followed by a sustained level that was approximately 50% higher than baseline. BK also transiently increased glucagon secretion with a peak that was 1.7-fold of the baseline concentration within 3 minutes, without a sustained secretion phase. BK caused a reduction in somatostatin secretion within 3 minutes to a level of 60% to 70% of the baseline concentration. The BK concentration of the rat pancreas was 3.42 +/- 1.45 micrograms/g protein (n = 5), which was approximately 3 mumol/L. We concluded that BK stimulated insulin secretion, transiently increased glucagon secretion, and decreased somatostatin secretion during the 30-minute perfusion of the rat pancreas.
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PMID:The effect of bradykinin on secretion of insulin, glucagon, and somatostatin from the perfused rat pancreas. 932 91

The body's general response to serious thermal injury is characterized by increased vascular permeability immediately after injury and subsequent hypovolemic shock. Skeleto-muscular proteolysis, lipolysis, gluconeogenesis, increased metabolic rate, and a severe systemic inflammatory response induced by local infections or surgical procedures. The increased vascular permeability is mediated by histamine and numerous vasoactive substances, including serotonin, bradykinin, prostaglandins, leukotrienes, and platelet activating factor. Hyper-metabolism is mediated by hormones such as catecholamines, glucagon, and particularly cortisol. In addition, among the putative mediators of the metabolic response to injury, attention has recently been focused on cytokines and lipid mediators which are mainly produced by activated reticuloendothelial cells. Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor and cortisol responses are interrelated, since cytokines activate the hypothalamo-adrenal axis. The cytokine storm seen in burn patients may be associated with depression of the immune system and with susceptibility to infection. Thermal injury can also lead to activation of the renin-angiotensin-aldosterone system, increased ADH production, and production of atrial natriuretic polypeptide to maintain the circulatory volume. Burn wound infections or surgical procedures can produce and perpetuate a mediator-induced systemic inflammatory response that may lead to multiple organ failure. Serum levels of interleukin-6 are very sensitive to surgical stress, and may be a useful indicator of the general condition of severely burned patients.
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PMID:[Pathophysiologic changes in patients with severe burns: role of hormones and chemical mediators]. 954 40

The first potent nonpeptidic ligands for somatostatin, luteinizing hormone-releasing hormone, glucagon and bradykinin receptors have been reported. Nonpeptidic clinical candidates have been identified or are currently under study for substance P, bradykinin, endothelin, growth hormone secretagogue, angiotensin, vasopressin, motilin and cholecystokinin. Design, screening, combinatorial chemistry and classical medicinal chemistry all played important roles in these advances.
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PMID:Nonpeptidic ligands for peptide and protein receptors. 1041 45

Diabetes is associated with endothelial dysfunction and increased risk of hypertension, cardiovascular disease, and renal complications. Earlier studies have revealed that hyperglycemia impairs nitric oxide (NO) production and diabetes causes endothelial dysfunction in humans and experimental animals. This study was designed to test the effects of altered concentrations of glucose, insulin, and glucagon, the principal variables in types I and II diabetes, on NO production and endothelial NO synthase (eNOS) expression in cultured human coronary endothelial cells. Cultured endothelial cells were incubated in the presence of glucose at either normal (5.6 mM) or high (25 mM) concentrations for 7 days. The rates of basal and bradykinin-stimulated NO production (nitrate + nitrite) and eNOS protein expression (Western blot) were then determined at the basal condition and in the presence of insulin (10(-8) and 10(-7) M), glucagon (10(-8) and 10(-7) M), or both. Incubation with a high-glucose concentration for 7 days significantly downregulated, whereas insulin significantly upregulated, basal and bradykinin-stimulated NO production and eNOS expression in cultured endothelial cells. The stimulatory action of insulin was mitigated by high-glucose concentration and abolished by cotreatment of cells with glucagon. Thus hyperglycemia, insulinopenia, and hyperglucagonemia, which frequently coexist in diabetes, can work in concert to suppress NO production by human coronary artery endothelial cells.
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PMID:Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression. 1089 17


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