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)

The effect of intrathecally (i.t.) applied substance P (SP) analogue, (D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nle 11)-SP (Spantide II), was examined in rats. Spantide II even at a high dose (10 micrograms) did not evoke any behavioural responses and caused no motor disturbances, but it did have a brief antinociceptive effect on the hot-plate test. Spantide II dose-dependently reduced the caudally directed scratching/biting behaviour, evoked by 1 microgram i.t. SP for over 30 min, but did not block the caudally directed scratching behaviour evoked by i.t. somatostatin. Histological examination revealed no pathological changes in the spinal cord after treatment with Spantide II. The results indicate that Spantide II is an effective tachykinin antagonist in the central nervous system and that it causes no neural damage.
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PMID:Antinociceptive and substance P antagonistic effects of intrathecally injected spantide II in rat: no signs of motor impairment or neurotoxicity. 169 80

A series of cyclic, conformationally constrained peptides related to somatostatin were designed and synthesized in an effort to develop highly selective and potent peptides for the mu opioid receptor. The following new peptides were prepared and tested for their mu opioid receptor potency and selectively in rat brain binding assays: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (2, CTOP); D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (3, CTAP); D-Phe-Cys-Tyr-D-Trp-Nle-Thr-Pen-Thr-NH2 (4); D-Phe-Cys-Tyr-D-Trp-Lys-Val-Pen-Thr-NH2 (5); D-Phe-Cys-Tyr-D-Trp-Lys-Gly-Pen-Thr-NH2 (6); D-Phe-Cys-Tyr-Trp-Lys-Thr-Pen-Thr-NH2 (7); D-Tyr-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH (8); D-PhGly-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (9); and D-PhGly-Pen-Phe-D-Trp-Lys-Thr-Cys-Thr-OH (10). The most selective peptide, 2 (CTOP), displayed both high affinity (IC50 = 3.5 nM) and exceptional selectivity (IC50 delta/IC50 mu = 4,000) for mu opioid receptors. Furthermore, 2 exhibited very low affinity for somatostatin receptors in the rat brain (IC50 greater than 24,000 nM), with an IC50 somatostatin/IC50 mu receptor selectivity of 8,750. These conformationally constrained cyclic peptides should provide new insight into the structural and conformational requirements for the mu opioid receptor and the physiological role of this receptor.
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PMID:Design and synthesis of conformationally constrained somatostatin analogues with high potency and specificity for mu opioid receptors. 287 79

Spiking activity of the gastrointestinal tract was recorded in 4 fasted pigs and 4 fasted dogs during the intravenous infusion at two rates, 5 (rate A) and 20 (rate B) ng . kg-1 . min-1 of 13-Nle-motilin, somatostatin, and bovine pancreatic polypeptide. Infusions continued for 2 h in pigs and for 5 h in dogs. 13-Nle-Motilin was unable to induce a migrating myoelectric complex or to modify its frequency in the pig at either rate of infusion. In contrast, the infusion of 13-Nle-motilin at rate B in the dog induced a migrating myoelectric complex but delayed the occurrence of the following migrating myoelectric complex. However, the mean duration (74 +/- 22 min) of the migrating myoelectric complex interval in the 5 h of infusion did not significantly change compared with the control period (92 +/- 8 min). At rate B, somatostatin inhibited the gastroduodenal spiking activity in the pig and disrupted the migrating myoelectric complex pattern, whereas this hormone at both rates of infusion increased the frequency of the migrating myoelectric complex by 69.3% and 17.2%, respectively, in the dog. The infusion of bovine pancreatic polypeptide increased the frequency of the migrating myoelectric complex significantly by 36.4% and 82% at rates A and B in the pig and by 148% at rate A in the dog. Bovine pancreatic polypeptide also inhibited spiking activity in the duodenum but not in the jejunum at rate B in the dog. These results suggest that pancreatic polypeptide, but not somatostatin, may have a regulatory function on the rhythmicity of the migrating myoelectric complex in the dog and pig and that motilin does not control the occurrence of duodenal migrating myoelectric complex in the pig.
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PMID:Effects of motilin, somatostatin, and pancreatic polypeptide on the migrating myoelectric complex in pig and dog. 612 39

Capsaicin-sensitive neurones release a number of neuropeptides, such as substance P, neurokinin A, somatostatin and calcitonin gene-related peptide (CGRP), which exert a number of effects on smooth muscle tissues. Endothelin-1 was thought to potentiate the capsaicin-evoked release of neuropeptides from sensory neurones of the rat. We have investigated the neuromodulatory effects of endothelin-1 on capsaicin-induced release of neurotransmitters from rat vas deferens. Capsaicin and human alpha calcitonin gene-related peptide (human alphaCGRP) reduced the rat vas deferens twitch responses induced by electrical field stimulation. Human beta calcitonin gene-related peptide-(8-37) [human betaCGRP-(8-37)] (1 microM), a selective alphaCGRP receptor antagonist, antagonized the inhibitory effects of both drugs. Endothelin-1 concentration dependently evoked an increase in basal tone of the musculature and potentiated the amplitude of the electrically stimulated responses, blocking inhibitory effects of capsaicin but not of human alphaCGRP. Moreover, endothelin-1 did not markedly change the inhibitory effects of papaverine (0.1-100 microM) or isoprenaline (1 nM-100 microM) on responses to electrical field stimulation. FR 139317 [(N,N-hexamethylene) carbamoyl-Leu-D-Trp(N-Me)-D-2-Pya], a selective endothelin ET(A) receptor antagonist, administered 30 min before endothelin-1 restored the capsaicin effects whereas BQ 788 [Dmpc-gamma-MeLeu-D-Trp-(1-methoxycarbonyl)-D-Nle], a selective endothelin ET(B) receptor antagonist, was completely ineffective. The endothelin-1-induced block of the capsaicin effect was resistant to tetrodotoxin (1 microM) and 30-min pre-treatment with MEN 10.627 (cyclo[(Met-Asp-Trp-Phe-Dap-Leu) cyclo (2beta-5beta)]), a selective tachykinin NK2 receptor antagonist, did not abolish the endothelin-1 effect on the inhibitory response to capsaicin. These results suggest that endothelin-1 selectively inhibits the capsaicin-induced release of neurotransmitters from rat vas deferens and these effects are mediated via endothelin ET(A) receptors but not by tachykinin release.
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PMID:Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens. 993 22

The cyclic somatostatin analogue cyclo[Pro(1)-Phe(2)-D-Trp(3)-Lys(4)-Thr(5)-Phe(6)] (L-363,301) displays high biological activity in inhibiting the release of growth hormone, insulin, and glucagon. According to the sequence of L-363,301, we synthesized a number of cyclic hexa- and pentapeptides containing nonnatural alpha- and beta-amino acids. The N- fluorenylmethoxycarbonyl protected cyclic beta-amino acid [1S, 2S, 5R]-2-amino-3,5-dimethyl-2-cyclohex-3-enecarboxylic acid (cbetaAA), for the replacement of the Phe(6)-Pro(1) moiety of L-363,301, was synthesized in two steps by an enantioselective multicomponent reaction using (-)-8-phenylmenthol as a chiral auxiliary. The resulting peptide cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] (Trt = triphenylmethyl) shows high antiproliferative effects in an in vitro assay with A431 cancer cells. The same peptide without the Trt group does not reveal any biological activity, whereas L-363,301 and closely related hexapeptides show only minor activity. By comparison of the solution structure of cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] with the structure of l-363,301, a nearly perfect match of the betaII'-turn region with d-Trp in the i + 1 position was observed. The cyclic beta-amino acid cbetaAA is likely needed for the bioactive conformation of the peptide.
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PMID:Structure-activity relationship studies optimizing the antiproliferative activity of novel cyclic somatostatin analogues containing a restrained cyclic beta-amino acid. 1582 30

The effects of camptothecin-somatostatin (CPT-SS) conjugates were investigated on small cell lung cancer (SCLC) cells. CPT was coupled to a SS agonist (SSA), c(Cys-Phe-DTrp-Lys-Thr-Cys)Thr-NH2 using the built in nucleophile assisted-releasing group (L1) N-methyl-aminoethyl-Gly-Dser-Nle-Dtyr-Dser or (L2) aminoethyl-Gly-Dser-Nle-Dtyr-Dser. The resulting CPT-L1-SSA and CPT-L2-SSA inhibited the specific binding of [125I-Tyr11]SS to NCI-H69 cell membranes with IC50 values of 0.2 and 2.1 nM, respectively. [125I]CPT-L1-SSA was internalized by SCLC cells at 37 degrees C but not at 4 degrees C. CPT-L1-SSA and CPT-L2-SSA inhibited in a dose-dependent manner the increase in adenylylcyclase activity caused by 25 microM forskolin. In vitro, 0.3 microM CPT-L1-SSA half-maximally inhibited the clonal growth of SCLC cells and 1 microM CPT-L1-SSA strongly inhibited 3H-thymidine incorporation into DNA and trypan-blue exclusion. These results suggest that CPT conjugated peptides such as CPT-L1-SSA may prove useful for exploring the efficacy of receptor-directed cytotoxicity to inhibit the proliferation of SCLC cells.
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PMID:Camptothecin-somatostatin conjugates inhibit the growth of small cell lung cancer cells. 1611 93