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)

Somatostatin inhibited secretin-stimulated cyclic AMP formation in pancreatic acinar cells. The inhibition was only partial. Maximal inhibition reached about 50%. Somatostatin analogs tested inhibited secretin-stimulated cyclic AMP formation with a lower potency than somatostatin. Cys-Aza Ala-Phe-Phe-DTrp-Lys-Thr-Phe-Phe-Cys was found to be an antagonist of somatostatin in inhibiting secretin-stimulated cyclic AMP. Analogs inhibited the binding of 125I-[Tyr11] somatostatin to pancreatic acini. There was a good correlation (r = 0.97) between concentration for inhibiting 50% secretin-stimulated cyclic AMP and receptor binding affinities.
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PMID:Somatostatin analogs: correlation of receptor affinity with inhibition of cyclic AMP formation in pancreatic acinar cells. 285 71

The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 micrograms SMS were injected sc, and plasma GH and insulin and blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P less than 0.001) decreased in seven of eight acromegalic patients from 30 +/- 5 (+/- SE) to an average of 10.7 +/- 4 micrograms/l from 1-10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P less than 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve (P less than 0.01), during the first 3 h after SMS administration. Circulating GH was not altered by SMS or the dopamine agonist mesulergine in one patient, but the combination of both substances (50 micrograms SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 PM, 0.1 nM, and 10 nM SMS or natural somatostatin exerted a similar inhibitory effect (12-39% reduction; P less than 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion, the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore, it may represent a useful tool in the chronic management of this condition.
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PMID:The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients. 286 Jan 19

The in vivo effects on tumour growth of a potent somatostatin analogue, SMS 201-995 [H-(D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Thr-(ol)], were measured in two characterised transplantable tumours: a) the Swarm rat chondrosarcoma, known to be insulin-, growth hormone (GH)-, somatomedin- and corticosteroid-dependent, b) a hamster insulinoma, bearing specific high affinity somatostatin receptors. SMS 201-995 (1.25 mg/kg/day) given for 25 days to rats bearing freshly transplanted chondrosarcomas inhibited tumour volume by 48%. A significant tumour growth inhibition was measured also in well developed tumours treated with high doses of SMS 201-995 (1.25mg/kg/day) for 7 days. In the treated animals, GH was significantly inhibited. In hamsters bearing a freshly transplanted insulinoma, the daily application of SMS 201-995 (200 micrograms/kg/day, sc) for 33 days could significantly inhibit the growth (as measured by tumour volume) of the tumour. A moderate inhibitory effect of SMS 201-995 on the growth of well grown insulinomas could also be observed. This study shows that SMS 201-995 under the present experimental conditions has a moderate but significant growth inhibitory effect in two different transplantable tumour models. In the rat chondrosarcoma, the effect of SMS 201-995 is probably indirect, due to inhibition of GH, somatomedin and insulin. In the hamster insulinoma, the effect is possibly due to a more direct action of SMS 201-995 on specific somatostatin receptors present in this tumour.
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PMID:A somatostatin analogue inhibits chondrosarcoma and insulinoma tumour growth. 286 Jul 68

The somatostatin antagonist analogue cyclo Ahep-Phe-D-Trp-Lys-Thr(Bzl) stimulates growth in young female rats, while somatostatin itself has only equivocal effects on inhibiting growth.
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PMID:Somatostatin antagonist analogue stimulates growth in rats. 286 50

It has been predicted on the basis of cDNA sequence analysis that anglerfish pancreatic islets contain at least two different preprosomatostatins (I and II). The C-terminal amino acid sequences of preprosomatostatin I and II were predicted to be identical to mammalian hypothalamic somatostatin-14 (SS-14) and its analog [Tyr7, Gly10]SS-14, respectively. That SS-14 is expressed in anglerfish pancreatic islets, has been shown earlier in pulse-chase experiments and by chemical characterization. However, it was observed that [Tyr7, Gly10]SS-14 was not expressed as such, but as part of larger polypeptides. Pulse-chase experiments combined with reverse-phase high pressure liquid chromatography, amino acid analysis with two different chromatographic systems, and complete Edman degradation indicated that preprosomatostatin II is processed in anglerfish islets to two different forms of somatostatin-28 (SS-28). The primary structure of the major form containing hydroxylysine (Hyl) was determined to be: H-Ser-Val-Asp-Ser-Thr-Asn-Asn-Leu-Pro-Pro-Arg- Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn-Phe-Tyr-Trp-Hyl-Gly-Phe-Thr-Ser-Cys-OH. The amino acid sequence of the minor form differs only at residue 23 by substitution of lysine for hydroxylysine. This is the first time that hydroxylysine, an amino acid which characteristically occurs in collagen or collagen-like structures has been identified in a potential regulatory peptide. It can be speculated that this amino acid is formed by post-translational hydroxylation of a lysine C-terminally linked to a glycine residue and thus modified at a site which has been recognized as hydroxylation site in collagen or collagen-like structures. The biological consequences of this unusual modification are being investigated.
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PMID:Anglerfish pancreatic islets produce two forms of somatostatin-28. 286 28

Pancreatic tissue of the channel catfish (Ictalurus punctatus) contains two somatostatins. The amino acid sequence of a 14-residue containing peptide (SS-14) is identical in sequence and has the same mass ion by fast atom bombardment mass spectrometry as mammalian SS-14. A 22-residue somatostatin (SS-22) has also been isolated and its amino acid sequence determined. The amino acid sequence differs from that reported by Oyama et al. (J Biol Chem 255:2251, 1980) in two of the 22-residues (positions 5 and 19). Somatostatin-22 is a glycoprotein, with carbohydrate attached at Thr-5. Several 22-residue peptides have been purified and all of them have identical amino acid compositions and different carbohydrate structure and/or composition. SS-22 has 7 amino acid residues which are identical to those observed in SS-14. The nucleotide sequence of the two cDNAs coding for SS-14 and SS-22 have been determined. The mRNAs encode precursors to SS-14 and SS-22 of 114 and 105 residues, respectively. The two precursors also have different amino acid sequence at the site of prohormone proteolytic processing. Analysis of genomic DNA reveals that SS-14 and SS-22 sequences are present on different restriction fragments and thus are encoded by separate genes.
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PMID:Somatostatins of the channel catfish. 286 31

The somatostatin analogs D-Phe-Cys-D-Trp-Lys-Thr-Cys-Thr and the corresponding penicillamine compounds have been prepared and tested for their ability to displace [3H]naloxone and [3H] [D-Ala2, D-Leu5]enkephalin from rat brain receptors. While somatostatin and the cystine containing peptide displayed little or no preference for either receptor system, the substitution of penicillamine at position two or seven resulted in analogs that displayed opposite receptor selectivity. The substitution of tyrosine for phenylalanine at position three resulted in a large increase in opiate receptor affinity which may be related to the known requirement for a phenolic hydroxyl moiety in the rigid opiate and enkephalin systems. Conformational properties of these analogs were also examined and related to their affinity for opiate and somatostatin receptors in the rat brain.
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PMID:Somatostatin analogs with affinity for opiate receptors in rat brain binding assay. 286 80

Somatostatin-like immunoreactivity (SLI) was purified from frog brain and retina, and the structure of the brain peptide was determined. Frog brain (101 g) and retinal (45 g) tissues were extracted with 3% acetic acid, yielding 9.6 and 0.44 nmol of SLI, respectively. SLI was further purified by chromatography on a somatostatin immunoaffinity column followed by sequential application to reverse-phase C-18 HPLC columns. The brain and retinal peptides, purified roughly 100,000-fold with net yields of 7.5 and 2.3%, respectively, appeared identical in the final steps of purification. The amino acid sequence of brain SLI, as determined by a gas-phase automated Edman degradation technique, was as follows: Ala-Gly-(Cys)-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-(Cys). Our data indicate that despite structural variations in somatostatins of other lower vertebrates, the amino acid sequence of frog brain and, by deduction, retinal SLI is identical to that of somatostatin tetradecapeptide. These findings support the physiological relevance of studies directed at elucidating the neurotransmitter function of somatostatin using the well-established models of frog brain and retina.
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PMID:Purification of somatostatin from frog brain: coisolation with retinal somatostatin-like immunoreactivity. 286 37

In the search for selective and long-acting analogs of somatostatin, nearly 200 compounds were synthesized by solid-phase methods, purified, and tested biologically. Among these octapeptides, some contained N-terminal (Formula: see text) were 177 times and 113 times more potent, respectively, than somatostatin in tests for inhibition of growth hormone release. These two octapeptides containing tyrosine and valine in positions 3 and 6, respectively, were more active and more selective than their Phe-3 and Thr-6 counterparts, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2. D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 was also about 6 times more potent than its L-Trp-4 diastereoisomer. The analogs D-Phe-Cys-Tyr-Lys-Val-Cys-Thr-NH2 and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 showed a prolonged duration of action and were able to inhibit growth hormone release for at least 3 hr. Analogs of both Phe-3/Thr-6 and Tyr-3/Val-6 classes also suppressed the release of insulin and glucagon in rats and pentagastrin-induced secretion of gastric acid in dogs, but their potencies in these tests were much smaller than the growth-hormone-release inhibitory activity. Some of these analogs possessed antitumor activities as shown by the inhibition of growth of animal models of prostate, mammary, and ductal pancreatic tumors.
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PMID:Synthesis and biological activity of highly potent octapeptide analogs of somatostatin. 286 90

A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3, 14-somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the synthesis of our most potent and selective mu opioid receptor compound D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 +/- 0.1) and exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.
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PMID:Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors. 287 70


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