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)

[3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies.
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PMID:Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones. 19 53

Female Wistar rats weighing 217 g were subjected to two types of surgical stress: uncomplicated (hysterectomy) and complicated (spleen and uterus ligated, crushed, and left in situ). Liver function as assessed by amino-N conversion was measured as the capacity for urea-N synthesis preoperatively (control animals) and on Days 1, 3, and 6 postoperatively. Uncomplicated surgery transiently increased the capacity for urea-N synthesis by 30% the first postoperative day (P less than 0.001). Complicated surgery decreased the capacity for urea-N synthesis to 55% throughout the investigation period (P less than 0.001). This was not due to a general change in liver mass since galactose elimination capacity remained constant. The increase in the capacity for urea-N synthesis after uncomplicated surgery is probably due to glucagon since plasma glucagon increased whereas plasma insulin and blood glucose remained unchanged after amino acid loading. The persistent decrease in the capacity for urea-N synthesis in complicated surgery is not due to changes in these regulators: glucagon increased, insulin decreased, and the rats were hypoglycemic. All changes are expected to increase the capacity for urea-N synthesis. The mechanism for the emergence of these two distinct metabolic patterns is not known. The phenomenon is probably important for interpretation of metabolic data on clinical stress.
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PMID:Contradictory effects of uncomplicated versus complicated abdominal surgery on the hepatic capacity for urea synthesis in rats. 220 48

Beta 2 adrenoceptors have been subdivided into beta 1 and beta 2 receptors, both by the varying response of different tissues to sympathomimetic amines and, more recently, by radioligand-binding techniques. It would appear that beta 1 receptors occur predominantly in the heart, whereas beta 2 receptors are found in lungs, peripheral blood vessels and uterus, and are also involved with glycogenolysis and glucagon and insulin secretion. In addition, the distribution of beta 1 receptors appears to relate to the density of sympathetic innervation of an organ or tissue, but tissues without sympathetic innervation are found to contain beta 2 receptors. Thus, beta 1 adrenoceptors may be considered as physiologically innervated receptors mediating responses to neuronally released norepinephrine, and beta 2 receptors as mediating responses to circulating catecholamines, particularly epinephrine. Radioligand-binding studies have also shown that the heart contains beta 2 receptors and the lung beta 1 receptors, but these are in the minority, and their role has not been identified. For many years, cardioselective beta 1-adrenoceptor antagonists have been available. This was considered to be a dose-dependent phenomenon but recent evidence has cast doubt on the concept that cardioselectivity is lost during dose increases within the therapeutic range. Nevertheless, even small doses of cardioselective drugs may show some beta 2-receptor antagonism, and may have adverse effects on patients with obstructive airways disease. Finally, nonselective drugs may result in a diastolic pressor effect in the presence of circulating catecholamines in contrast to the "vascular sparing" seen with cardioselective drugs.
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PMID:Pharmacologic aspects of cardioselectivity in a beta-blocking drug. 288 70

Inhibitor-1 purified from rabbit liver could not be distinguished from the skeletal muscle protein by chromatographic, electrophoretic and immunological criteria. Amino acid sequences comprising 68% of rabbit liver inhibitor-1 were identical to the skeletal muscle protein indicating that they are products of a single gene. Total inhibitor-1 activity in heat-treated rabbit liver extracts was similar to that in skeletal muscle extracts, and the phosphorylation state of inhibitor-1 increased from 14% to 42% in rabbit liver in vivo after an intravenous injection of glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-1 recognised a single major protein of identical electrophoretic mobility (26 kDa) in each rabbit tissue examined (skeletal muscle, liver, brain, heart, kidney, uterus and adipose). The antibodies also recognised a single major (30 kDa) protein in the same rat tissues, except liver. The results show that while there are interspecies differences in apparent molecular mass, inhibitor-1 is likely to be the same gene product in each mammalian tissue. Inhibitor-1 was not detected in rat liver, either by activity measurements or immunoblotting, irrespective of the age, sex or strain of the animals. Immunoblotting also failed to detect inhibitor-1 in mouse liver, although it was present in guinea pig, porcine and sheep liver. The absence of inhibitor-1 in rat liver indicates that phosphorylation of this protein cannot underlie the increased phosphorylation of hydroxymethylglutaryl-CoA reductase observed after stimulation by glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-2 recognised a 31 kDa protein in each rabbit tissue, and a 33 kDa protein in all rat tissues including liver. The results suggest that inhibitor-2 is the same gene product in each mammalian tissue.
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PMID:Partial structure and hormonal regulation of rabbit liver inhibitor-1; distribution of inhibitor-1 and inhibitor-2 in rabbit and rat tissues. 291 4

The potential contributions of placental extraction and degradation to glucoregulatory hormone turnover in late pregnancy were assessed by measuring arteriovenous differences for glucose, insulin, glucagon and human placental lactogen (hPL) across the uterine and fetal circulation in ten pregnant women at the time of elective caesarean section. The observations were made during stable conditions of euglycaemia; values for maternal arterial glucose, insulin, glucagon and hPL were 78.8 +/- 5.0 mg/dl, 10.1 +/- 2.1 microU/ml, 72.0 +/- 8.5 pg/ml and 5.18 +/- 0.59 micrograms/ml, respectively. The glucose decrements observed consistently across the uterus and fetus indicated uptake by the placenta and fetus, and in the maternal circulation the arterial-uterine vein increment for hPL was 2.10 +/- 0.44 micrograms/ml. However, within the limits of analytical accuracy, no significant gradient could be demonstrated for insulin across the uterine (maternal) or umbilical (fetal) circulations. A small (8.5 per cent) but significant arteriovenous difference for glucagon was observed across the uterus but none was found on the fetal side of the placenta. The findings indicate that detectable gradients for insulin cannot be demonstrated under basal conditions of metabolism and at normal rates of placental blood flow. The results do not exclude the possibility of more significant extraction ratios under other physiological conditions or at higher concentrations of glucoregulatory hormones.
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PMID:Transplacental arteriovenous gradients for glucose, insulin, glucagon and placental lactogen during normoglycaemia in human pregnancy at term. 390 31

Prostaglandins, the hydroxy unsaturated C20 fatty acids, are found throughout the body and have an equally wide range of biological activities. Prostaglandins are known to: 1) stimulate uterine contraction; 2) inhibit spontaneous contraction of the rabbit uterus; 3) inhibit the respiratory smooth muscle of different animals; 4) lower systemic arterial blood pressure when injected intravenously; 5) stimulate contractions in isolateral segments of intestinal smooth muscle of most species investigated; 6) produce transient sedation when intravenously injected in cats, and 7) inhibit lipolysis induced by catechal amines, corticotrophin, glucagon and thyroid stimulating hormone. The inhibitory and excitatory effects of prostaglandins may each have a physiological importance at different sites. Current state of knowledge of the distribution, metabolism and actions of the prostaglandins is still fragmentary. The functional significance of the prostaglandins is yet to be determined.
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PMID:Biological activities of pure prostaglandins. 531 39

The immunogold-silver staining technique is shown to be of great value in the detection of regulatory peptide-containing nerves and endocrine cells in routinely fixed, paraffin-wax-embedded tissues. The method appears to be better for this system than peroxidase anti-peroxidase (PAP) which can yield poor or variable results. Antibodies to regulatory peptides, including calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), glucagon, pancratic polypeptide, and somatostatin 14 and 28, as well as to neurofilaments, neuron-specific enolase (NSE) and S-100, were used on sections of a variety of tissues from rat and pig including respiratory tract, skin, gut, pancreas, vagina, uterus, fallopian tube and kidney. In all cases, stronger immunostaining of nerves was obtained with the immunogold-silver technique than with PAP. The inherent density of the staining was also found to improve the visibility of endocrine cells in the section, and to permit the use of routine histological stains for counterstaining. As immunogold-silver staining is sensitive, rapid, cheap and avoids hazardous reagents, we feel it has great potential for the immunostaining of nerves and endocrine cells that contain regulatory peptides in routinely fixed and embedded tissues and may prove useful in pathology.
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PMID:The potential of the immunogold-silver staining method for paraffin sections. 608 58

Capsaicin (CAP) has been shown to exert a selective neurotoxic effect on peptidergic primary afferent neurons. The effect of CAP on the isolated guinea-pig left auricle and papillary muscle preparations and on the isolated rat uterus was used to elucidate its mode and site of action with regard to cellular Ca2+ utilization. In the electrically driven left auricle CAP first increased and then decreased the size of the contractions while in the electrically driven papillary muscle CAP caused only a decrease in the contractions. Electrophysiological measurements showed that the initial increase in contraction size coincided with a decrease in the upstroke velocity of the action potential. This membrane-stabilizing effect of CAP seemed also responsible for the decrease in contractile activity. The positive inotropic effect of CAP on the left auricle was concentration-dependent (0.03-6.5 microM). The positive inotropic effect of 0.33 microM CAP was reproducible at intervals of 15 min, whereas tachyphylaxis developed at shorter intervals or higher concentrations of CAP. The percent increase in the size of contractions by 0.33 microM CAP was smaller when [Ca2+]e was doubled but larger when 2.2 microM verapamil or 0.1 mM La3+ was present. The increase in contractions by 0.4-400 microM isoproterenol was greatly reduced by 0.33 microM CAP in a noncompetitive manner. The positive inotropic effect of 2.9 microM glucagon was also inhibited by 0.33 microM CAP. In the isolated anoestrous rat uterus 0.03-3.3 microM CAP caused a transient inhibition of the spontaneous contractions similarly to the effect of 2.2 microM verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A study of the mode and site of action of capsaicin in guinea-pig heart and rat uterus. 647 86

A dose-dependent increase in body length and weight can be induced in Snell dwarf mice by human, porcine and bovine growth hormones, ovine prolactin, bovine TSH, T4 and T3, and to a lesser extent by insulin. In contrast, porcine FSH, equine LH, testosterone, oestradiol and glucagon influenced neither body length nor weight. Beside body length and weight, the weight of many organs is stimulated by hormonal treatment. GH, T4 and T3 have a rather similar spectrum of effects, with exceptions for the skinfold and epididymal fat-pads. LH had no effect, but in contrast FSH had a strong effect on the seminal vesicles and a less pronounced one on the testis. Oestradiol induced a marked enlargement of the uterus, whereas testosterone increased the weights of the kidneys and seminal vesicles. The main action of insulin is probably localized on body fat. Glucagon, however, did not stimulate organ growth. These data illustrate again the complexity of hormonal regulation of growth.
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PMID:The effects of pituitary, thyroid, pancreatic and sexual hormones on body length and weight and organ weights of Snell dwarf mice. 672 29

Vasoactive intestinal peptide (VIP) has been shown to stimulate adenylyl cyclase activity in human endometrial membranes. The effect was dependent on the time and temperature of incubation as well as on the concentration of endometrial membrane proteins in the medium. In the presence of 1 microM GTP, half-maximal stimulation of adenylyl cyclase activity was observed at 25.0 +/- 7.0 nM VIP, whereas the maximal activity (at 1 microM VIP) corresponded to an increase of about 140% with respect to basal values (7.5 +/- 0.6 pmol cyclic AMP/min/mg of protein). However, the maximal stimulation of adenylyl cyclase activity was obtained with helodermin (1 microM) that increased the activity by 170% over the basal. The relative potency of VIP-related peptides upon the adenylyl cyclase activity was: helodermin (ED50 = 1.8 +/- 1.4 nM) > VIP (ED50 = 25.0 +/- 7.0 nM) > PHI (ED50 = 725.0 +/- 127.2 nM). Secretin had a faint effect upon the adenylyl cyclase activity and glucagon was completely inefficient at this level. The presence of alpha s and alpha i subunits of G proteins in human endometrium was detected by immunoblot. Preliminary results showed the presence of two classes of 125I-VIP receptors in human endometrial membranes with the following stoichoimetric parameters: high affinity receptor (Kd = 2.0 nM, binding capacity 0.1 pmol VIP/mg protein) and low affinity receptor (Kd = 0.43 microM, binding capacity 13.1 pmol VIP/mg protein). The present results together with the known presence of VIP in human uterus and the actions of this neuropeptide in the adjacent myometrial tissue support the idea that VIP and related peptides may have a role in human endometrium.
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PMID:Stimulation of the adenylyl cyclase activity in human endometrial membranes by VIP and related peptides. 839 8


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