Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By using only reverse-phase h.p.l.c., three fragments of prosomatostatin were isolated from an extract of a human pancreatic neuroendocrine tumour that produced somatostatin, vasoactive intestinal polypeptide and gastrin-releasing peptide. The amino acid composition of the peptides indicated that they represented prosomatostatin-(1-63)-peptide, prosomatostain-(65-76)-peptide and prosomatostatin-(79-92)-peptide (somatostatin-14). The identity of prosomatostatin-(1-63)-peptide was confirmed by characterization of the products of digestion with Armillaria mellea (honey fungus) proteinase. Partial micro-sequencing of prosomatostatin-(1-63)-peptide showed that the Gly24-Ala25 bond of preprosomatostatin was the site of cleavage of the signal peptide. Thus human prosomatostatin is a protein of 92 amino acid residues that is proteolytically cleaved in a pancreatic tumour at the site of a dibasic-residue (arginine-lysine) processing site and at a single-monobasic-residue (arginine) processing site.
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PMID:Characterization of three peptides derived from prosomatostatin [prosomatostatin-(1-63)-, -(65-76)- and -(79-92)-peptides] in a human pancreatic tumour. 289 3

The cyclostomes represent the first class of vertebrate in evolution to develop an endocrine pancreas. Two peptides with somatostatin-like immunoreactivity were isolated from the islet organ of one such cyclostome, the Atlantic hagfish (Myxine glutinosa). The primary structure of the more abundant peptide was established as: Ala-Val-Glu-Arg-Pro5-Arg-Gln-Asp-Gly-Gln10-Val-His-Glu-Pro- Pro15-Gly-Arg-Glu-Arg-Lys20-Ala-Gly-Cys-Lys-Asn25-Phe- Phe-Trp-Lys-Thr30-Phe-Thr-Ser-Cys. The second peptide, comprising 27% of the total immunoreactivity in the islet extract, was identical to mammalian somatostatin-14. The pathway of posttranslational processing of prosomatostatin in the hagfish islet differs markedly from the pathway in the higher vertebrates. In the mammalian pancreas, prosomatostatin is cleaved at the site of the single arginyl residue (corresponding to position 6 in hagfish somatostatin-34) and at the arginine-lysine site (corresponding to positions 19 and 20 in the hagfish peptide) to generate somatostatin-14 and somatostatin-28(1-12)-peptide. In the hagfish islet, Arg6 is not used as a cleavage site and cleavage at Arg19-Lys20 represents only a minor pathway of processing. The data provide further evidence of the strong evolutionary pressure to conserve the complete amino acid sequence of somatostatin-14.
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PMID:Primary structures of somatostatins from the islet organ of the hagfish suggest an anomalous pathway of posttranslational processing of prosomatostatin-1. 289 18

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.
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PMID:Studies on the mechanism of salicylate-induced increase of insulin secretion in man. 290 99

Lys-beta-urogastrone, an analogue of human beta-urogastrone with an additional N-terminal lysine, was shown to have similar effects in mice and sheep to mouse epidermal growth factor (mEGF). Lys-beta-urogastrone in doses of 0.18-3.24 micrograms g-1 body weight caused both precocious separation of eyelids and eruption of incisors in neonatal mice. In 17 sheep, intravenous infusion of the urogastrone analogue over c. 24 h led, towards the end of infusion, to erythema of the muzzle, caused reductions in voluntary food intake (with doses greater than or equal to 50 micrograms kg-1) and generally easier manual harvesting of the fleece (with infusions greater than or equal to 81 micrograms kg-1), with spontaneous shedding of the fleece (c. 14 days after infusions of greater than or equal to 116 micrograms kg-1). In five sheep infusions of 25, 38, 50, 83 and 118 micrograms kg-1 fleece-free body weight, plasma concentrations of lys-beta-urogastrone were near maximal 20 h after the infusions started and were, respectively, 1.1, 1.7, 5.5, 18 and 79 micrograms l-1 plasma. Plasma concentrations of gastrin, somatostatin and pancreatic polypeptide were determined in these five sheep. Plasma gastrin rose sixfold by the end of infusions of 25 micrograms kg-1 of the urogastrone analogue, and tenfold with the higher doses of infusion. Although plasma somatostatin concentrations were variable, a consistent trend was observed; lower levels were apparent during the lys-beta-urogastrone infusions. There was no discernible trend in pancreatic polypeptide concentrations.
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PMID:Effects of lys-beta-urogastrone in vivo. 290 24

The hormonal regulation of thyroglobulin synthesis has been studied using two independent clones of the OVNIS 6H cell line. Insulin, hydrocortisone and TSH were able to stimulate thyroglobulin synthesis, whereas transferrin, somatostatin and glycyl-histidyl-lysine were without effect. Insulin stimulated thyroglobulin synthesis without affecting cAMP production. Hydrocortisone, when combined with insulin was a stimulator too; this stimulation was not accompanied by an increase in cAMP. TSH alone was unable to stimulate either cAMP or thyroglobulin synthesis. The stimulatory effect of TSH on thyroglobulin synthesis took place only when combined with insulin or insulin plus hydrocortisone, and was mediated by cAMP. Consequently, insulin and hydrocortisone stimulated thyroglobulin synthesis by cAMP-independent mechanisms, whereas TSH acted via the cAMP system. Forskolin mimicked TSH effects on cAMP and thyroglobulin synthesis. Calf serum inhibited cAMP and thyroglobulin production. Optimal cAMP and thyroglobulin synthesis as well as TSH responsiveness were obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.
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PMID:cAMP dependent and independent regulation of thyroglobulin synthesis by two clones of the OVNIS 6H thyroid cell line. 304 Apr 95

Intrathecal (IT) injection of arginine vasopressin (AVP) in rats caused a transient (less than 30 min), dose-related paralysis of the hindlimbs, loss of hindlimb and tail nociceptive responsiveness, and increased mean arterial pressure. Motor dysfunction was produced with comparable potency by lysine vasopressin (LVP) and arginine vasotocin (AVT); oxytocin (OXY) was approximately 1000 times less potent. Paralysis induced by these peptides was selectively blocked following IT pretreatment with 0.5 nmoles of the vasopressin V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] Arg8-vasopressin (d(CH2)5[Tyr(Me2)]AVP). Pressor and antinociceptive responses to AVP were also blocked by this compound. However, at higher doses (2-5 nmoles, IT), d(CH2)5[Tyr(Me2)]AVP produced hindlimb paralysis, antinociception, and pressor responses by itself. In contrast to the fiber degeneration, cell loss, and necrosis found in lumbosacral cords of rats persistently paralyzed by other peptides (dynorphin A, somatostatin, and ICI 174864), neuropathological changes were not evident in spinal cords of rats transiently paralyzed by IT AVP. These results indicate that AVP-related peptides affected diverse spinal cord functions through interactions with a V1-like receptor. The similar pattern of cardiovascular and antinociceptive responses to other peptides (dynorphin A, somatostatin, and ICI 174864), which also caused hindlimb paralysis, suggests that the former responses may actually reflect the nonselective consequences of a peptide-induced disruption of spinal cord function, rather than specific shared pharmacological effects.
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PMID:Hindlimb paralytic effects of arginine vasopressin and related peptides following spinal subarachnoid injection in the rat. 324 52

Human thyroid cells were grown and subcultured in vitro to examine their responses to known hormones and growth factors, and to serum. The cells were obtained from surgical specimens and were either neoplastic or nonneoplastic. The effects of culture conditions on cell growth were measured by changes in cell numbers and by stimulation of [3H]thymidine incorporation. The results showed that serum (0.5%) was essential for cell proliferation, and that a mixture of insulin (10 micrograms/ml), transferrin (5 micrograms/ml), hydrocortisone (10 micrograms/ml), somatostatin (10 ng/ml), and glycyl-histidyl-lysine (10 ng/ml) enhanced the effect of serum. Maximum growth of the cells was obtained when epidermal growth factor was present at 10(-9) M. Differentiation was measured by production of thyroglobulin, which was found to be stimulated by thyrotropin. This system provides a means to study the hormonal control of growth and differentiation in human thyroid cells.
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PMID:Growth and differentiation in cultured human thyroid cells: effects of epidermal growth factor and thyrotropin. 351 Oct 27

The classical conversion site in precursors of regulatory peptides is a sequence of two basic amino acids. During recent years, however, a group of monobasic cleavage sites has emerged. In certain cell systems it has been shown that the monobasic cleavage mechanism is both a specific mechanism which only attacks a particular basic residue, and a distinct mechanism which can be separated from the dibasic cleaving mechanism within the same cell. The vast majority of monobasic cleavages occur at single arginines although cleavage after a lysine residue has also been demonstrated. There is no 'consensus sequence' of amino acids surrounding the single basic residue which is the apparent signal for proteolytic processing. However, in approximately one third of the cases, a proline residue is found either just before or just after the basic residue. On the basis of this 'proline-directed arginyl cleavage' it is discussed how the conformation of the peptide backbone might be important for this type of cleavage. Finally, it is suggested that tissue-specific expression of different processing enzymes, e.g. dibasic and monobasic specific forms, might explain the tissue-specific processing of precursors like the pro-opiomelanocortin and the CKK and somatostatin precursor.
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PMID:The processing of peptide precursors. 'Proline-directed arginyl cleavage' and other monobasic processing mechanisms. 351 23

Rat brain aminopeptidase activity was solubilized from membranes by incubation with thiols. This novel procedure resulted in the release of the same two aminopeptidases (MI and MII) previously shown to be solubilized by the nonionic detergent Triton X-100. The solubilized aminopeptidases MI and MII were resolved by ion-exchange chromatography and further purified by hydroxylapatite chromatography. Aminopeptidase MI was shown to hydrolyze only the beta-naphthylamides of arginine and lysine whereas aminopeptidase MII exhibited a broad specificity with respect to amino acid beta-naphthylamides. Only aminopeptidase MII hydrolyzed Leu-enkephalin at a significant rate, indicating that this enzyme can account for the membrane-bound enkephalin aminopeptidase activity. The enkephalin-degrading aminopeptidase is potently inhibited by opioid (alpha-neo-endorphin and dynorphin) as well as nonopioid (substance P, somatostatin, and angiotensin I) peptides in the range of 0.2-2.0 microM. The regional distribution of aminopeptidases MI and MII in rat brain are rather different, with aminopeptidase MII distribution more closely paralleling the distribution of opiate receptors.
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PMID:Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. 388 43

Primary cultures of rat thyroid cells were made in medium supplemented with 0.1--0.5% calf serum and containing six hormones or growth factors: insulin, thyrotropin, transferrin, hydrocortisone, somatostatin, and glycyl-L-histidyl-L-lysine acetate. The FRTL strain was purified by successive colonial isolations and was found to maintain highly differentiated features (secretion into the culture medium of physiological amounts of thyroglobulin and concentration of iodide by 100-fold). The FRTL strain has been observed for more than 3 years in continuous culture. It has maintained the same biochemical and morphological characteristics that typified the primary cultures of thyroid follicular cells immediately after their enzymatic release from the rat thyroid. Thyroid epithelial cells that were grown under more conventional cell culture conditions failed to retain these specialized characteristics. We show that maintenance in vitro of these specialized functions of rat thyroid follicular cells is dependent on low serum concentrations and supplementation with hormones in the primary cultures. Our observations indicate that this culture strategem may be aplicable to the general problem of maintenance of differentiated characteristics in cultures of other epithelial cells.
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PMID:Culture of hormone-dependent functional epithelial cells from rat thyroids. 610 91


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