Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Hypothalamic growth hormone-releasing factors (GRFs) have been purified recently from human pancreatic (hp) tumours and from rat hypothalamus (rh). GRF peptides have strong homology with peptides of the glucagon, vasoactive intestinal polypeptide and PHI-27 family. Aside from their potent actions on release of somatotropin, no other biological actions of GRFs have been reported. GRF has been localized in neurones bordering the ventromedial hypothalamic nucleus, a region associated frequently with experimental analysis of feeding behaviour. We now report that intracerebroventricularly (i.c.v.)-administered rhGRF and hpGRF(1-40) in doses of 0.2, 2.0 and 20.0 pmol, produced an increase in food intake in hungry rats. This effect seemed to be specific to GRF as i.c.v. injections of a structurally related but physiologically inactive peptide in the same doses had no effect on feeding. In addition, peripheral injections of rhGRF or growth hormone had no effect on food intake, suggesting that the present effects may be mediated centrally. Injections (i.c.v.) of rhGRF (0.2, 2.0 and 20.0 pmol) had no effect on general activity, suggesting that GRF does not produce nonspecific arousal.
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PMID:Stimulation of food intake in rats by centrally administered hypothalamic growth hormone-releasing factor. 391 14

The correspondence schemes for the amino acid sequence families from different animal species for two superfamilies of protein-peptide hormones and their precursors, i.e., proinsulin-IGF-prorelaxin and proglucagon-pro (PHM-VIP)-prosomatocrinin, were constructed. These schemes were used for the local intra- and interfamilial comparison of the sequences; the average profiles of hypothetical secondary structure of individual sites of these sequences according to Chow and Fasman were obtained, and the profiles of their physico-chemical properties (e. g., hydrophobicity and volume of side amino acid radicals) were computed. An analysis of the profiles obtained demonstrated that despite the apparent similarity of the tertiary structure of IGF and relaxin, on the one hand, and of insulin, on the other, the latter is devoid of the insulin-like receptor (effector) site, whereas in the case of IGF, this site is modified by additional links of the peptide chain. Based on the reciprocal comparison of prosomatocrinin with proglucagon and pro (PHM-VIP), it was assumed that the C-terminal fragment of prosomatocrinin separated from somatocrinin by a single arginine residue is a second glucagon-like peptide in the precursor molecule, which apparently possesses a biological activity.
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PMID:[Computer bank of amino-acid sequences of protein hormones. Analysis of evolutionary, conformational and physico-chemical properties of the individual sites of sequences in superfamilies of proinsulin and proglucagon]. 391 76

A single acute IV injection (1 microgram/kg) of the synthetic replicate of Somatocrinin (GRF) in 40 children with growth hormone (GH) deficiency induces a marked plasma GH increase, although heterogeneous. Clinical tolerance is excellent. Compared to Propranolol + Glucagon (P + G), GRF induces a better GH response. It also discriminates better idiopathic GH deficiency (n = 13), where mean GH peak = 6.5 ng/ml (3.3 after P + G) from GH deficiency secondary to a brain tumor (n = 24) where mean GH peak = 15.5 ng/ml (5.0 after P + G) GRF induces a slight Prolactin (Prl) increase, more obvious when basal Prl is elevated. However there is no correlation between GH and Prl responses to GRF even with basal hyperprolactinemia. GH response to GRF seems to slowly decrease after radiation therapy. GRF is a new potent, well tolerated secretagogue of GH and improves the diagnostic quality of the etiology of GH deficiency.
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PMID:[Somatocrinin and children in 1984. Application to the etiological diagnosis of somatotropin deficiencies]. 392 94

We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.
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PMID:Effect of growth hormone-releasing factor on plasma growth hormone, prolactin and somatomedin C in hypopituitary and short normal children. 392 75

We have studied the responsiveness of vascular adenylate cyclase to vasoactive intestinal peptide (VIP) and parathyroid hormone (PTH) using preparations of cerebral microvessels and arteries. Cerebral microvessels obtained from rats, guinea-pigs, cattle, and pigs all responded potently to bovine (b) PTH-(1-34), whereas considerable between-species variability was observed in the responsiveness to VIP. The homologous peptide to VIP, PHI (porcine heptacosapeptide), stimulated adenylate cyclase in both rat microvessels and a broken-cell preparation of bovine arteries. The ED50 values for activation of bovine arterial adenylate cyclase by VIP, PHI, and bPTH-(1-34) were 6.9 nM, 10 nM, and 100 nM, respectively, with the following order of efficacy: VIP = PHI greater than bPTH-(1-34). The other related peptides, hpGRF (human pancreatic growth hormone releasing factor), secretin, and glucagon, and the fragment VIP-(10-28) were inactive. The PTH antagonist, [Nle8, Nle18, Tyr34]bPTH-(3-34) amide, inhibited bPTH-(1-34) activation of vascular adenylate cyclase but did not affect activation by VIP using either microvessels or arteries. VIP or PHI demonstrated an additive effect with bPTH-(1-34) on vascular adenylate cyclase activity. However, the effects of VIP and PHI were nonadditive with each other. These data suggest that VIP and bPTH-(1-34) activate cerebral vascular adenylate cyclase by interacting with pharmacologically distinct receptors, whereas PHI and VIP likely interact with a common receptor.
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PMID:Cerebral vascular adenylate cyclase: evidence for coupling to receptors for vasoactive intestinal peptide and parathyroid hormone. 608 40

The binding of radiolabeled glucagon to rat brain membranes was investigated. Regional distribution studies indicate higher specific binding of 125I-labeled monoiodoglucagon to olfactory tubercule, hippocampus, anterior pituitary, and amygdala membranes, with somewhat lower binding to membranes from septum, medulla, thalamus, olfactory bulb, and hypothalamus. 125I-labeled glucagon bound to rat brain synaptic plasma membrane fractions with high affinity (KD = 2.24 nM). Specific binding was greater to synaptosomal membrane fractions relative to myelin, mitochondrial nuclear, or microsomal fractions. Inclusion of 0.1 mM GTP in the binding assay reduced the glucagon binding affinity (KD = 44.5 nM). Several neuropeptides and other neuroactive substances tested did not affect binding of labeled glucagon to brain membranes. Three different glucagon analogs inhibited labeled glucagon binding. Synthetic human pancreatic growth hormone-releasing factor, hpGRF-44, also inhibited binding, although the concentration required for half-maximal displacement was 100-fold higher than for native glucagon. Addition of glucagon to brain membranes resulted in approximately equal to 3-fold maximal activation of adenylate cyclase over basal levels. Glucagon at a concentration of 4.74 nM was required for half-maximal activation of pituitary membrane adenylate cyclase. These findings provide evidence for rat brain binding sites that respond to the pancreatic form of glucagon and can transduce this binding into the activation of adenylate cyclase.
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PMID:Identification of glucagon receptors in rat brain. 608 21

A growth hormone releasing factor of a human pancreatic islet tumor (hpGRF) of an acromegalic patient was purified and subjected to Edman degradation in a spinning cup sequencer. Approximately 0.7-1.2 nmol of peptide was applied to the cup without any pretreatment, after coupling to 3-sulfophenyl isothiocyanate or after cleavage with cyanogen bromide, staphylococcal protease, or trypsin. On the basis of the analytical data, the N-terminal sequence of 39 residues is established to be H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn- Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys- Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser- Asn-Gln-Glu-Arg-Gly-. It is proposed that alanine is residue 40 and represents (as free acid) the C terminus of hpGRF. Synthetic hpGRF(1-40)-OH is highly potent in stimulating GH secretion from the rat anterior pituitary in vitro and in vivo. The C-terminal sequence of hpGRF does not appear to contribute significantly to the biologic intrinsic activity and potency of hpGRF, as demonstrated by the fact that the natural product and the synthetic peptides hpGRF(1-40)-OH, hpGRF(1-40)-NH2, and hpGRF(1-29)-NH2 show equivalent in vitro activities. On the basis of sequence homologies, hpGRF is closely related to members of the glucagon secretin family, especially to the porcine gut peptide PHI.
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PMID:Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumor. 629 53

Secretin, a gut-brain peptide, elicited cyclic AMP production in a clone of neuroblastoma cells derived from the C1300 mouse tumor. Adenylate cyclase (EC 4.6.1.1) in plasma membranes from these cells was stimulated by secretin greater than vasoactive intestinal peptide greater than peptide histidine isoleucine amide, but not by the related peptides glucagon, gastric inhibitory polypeptide, or human growth hormone releasing factor. Hill coefficients for stimulation approximated one and the response to submaximal peptide concentrations was additive, as expected for hormones competing for a single receptor associated with the enzyme. Binding of 125I-labeled secretin to the neuroblastoma plasma membranes was saturable, time-dependent, and reversible. The KD determined from kinetic and equilibrium binding studies approximated 1 nM. The binding site displayed marked ligand specificity that paralleled that for stimulation of adenylate cyclase. The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin. These findings demonstrate the functional association of the secretin receptor with adenylate cyclase in neuronally derived cells.
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PMID:Secretin receptors on neuroblastoma cell membranes: characterization of 125I-labeled secretin binding and association with adenylate cyclase. 632 61

Synthetic human pancreatic growth hormone-releasing factor containing 40 amino acids ([hpGRF (1-40)]-OH) significantly stimulated plasma growth hormone (GH) levels in both sodium pentobarbital and urethane anesthetized rats. Synthetic secretin, gastric inhibitory polypeptide (GIP), and glucagon significantly decreased plasma GH levels while synthetic vasoactive intestinal peptide (VIP) had no effect. Secretin and GIP also altered the in vivo plasma GH response to [hpGRF(1-40)]-OH. Whether this effect is the result of an interaction at the pituitary level or is due to an extra-pituitary effect of secretin and GIP awaits further study.
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PMID:Effects of secretin and gastric inhibitory polypeptide on human pancreatic growth hormone-releasing factor(1-40)-stimulated growth hormone levels in the rat. 640 44

Synthetic human pancreatic GRF (hpGRF-44) was administered as an iv bolus to 28 normal children with short stature and 27 patients with GH deficiency. After a dose of 1 or 2 micrograms hpGRF-44/kg BW, mean plasma GH levels peaked at 15 and 30 min, respectively, with corresponding values of 30.1 +/- 4.7 and 33.2 +/- 3.7 ( +/- SE) ng/ml in normal but short children. The overall plasma GH response was greater than that of other GH stimulation tests such as insulin-induced hypoglycemia, glucagon-propranolol or L-dopa administration. Plasma LH, FSH, TSH, PRL, and cortisol levels were not altered by hpGRF-44 injection. Sixteen of 27 patients with GH deficiency did not respond to a 2 micrograms/kg BW hpGRF-44. However, plasma GH increases to greater than 5 ng/ml occurred in the remaining 11 patients. Their GH levels reached peaks between 15 and 90 min, with values ranging between 5.8 and 17.8 ng/ml. Two of these responding patients were infused iv with hpGRF-44 at 2.5 micrograms/min for 90 min after receiving an iv bolus injection of 2 micrograms/kg BW. Their plasma GH levels increased and remained near peak values throughout the infusion period. However, no increase in plasma GH levels occurred after a second bolus injection of hpGRF-44 given at the end of the infusion. These results suggest that hpGRF-44 is useful for the diagnosis of GH deficiency in individuals with short stature and that some patients with GH deficiency, diagnosed on the basis of established tests, have GH responses to hpGRF-44.
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PMID:Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism. 642 Apr 32


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