| 2863231 |
Hexapeptide analogue of somatostatin, Sandoz 201-456. Conformational study in dimethylsulfoxide by 1D and 2D n.m.r. methods |
None |
Int J Pept Protein Res |
Hexapeptide analogue of somatostatin, Sandoz 201-456. Conformational study in dimethylsulfoxide by 1D and 2D n.m.r. methods
Abstract
- The conformational properties of the somatostatin analogue 201-456 (1) have been studied by high field n.m.r. in DMSO. This analogue is the base structure of nine derivates synthesized by Bauer et al. and shows a very low biological activity, although derived structures such as SMS 201-995 (2) are very potent. Our study has shown an important difference between the most stable conformation of the two compounds: although the beta turn type II' structure at the Phe3-Trp4-Lys5 level is present in both analogues, an important conformational change appears at the cystine bridge. In SMS 201-995 the beta turn/beta sheet conformation is stabilized by the additional amino-acids D-Phe1 and Thr8 (ol) through intramolecular H-bonds."
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| 2863780 |
Comparative activity of memory-modulating neuropeptides before and after electric shock in white rats |
10.1007/BF01182994. |
Neurosci Behav Physiol |
Comparative activity of memory-modulating neuropeptides before and after electric shock in white rats
Abstract
- Neuropeptides are shown to exert a powerful influence on mnestic processes. They actively eliminate phenomena of electric-shock amnesia, the strongest agent here being arginine vasopressin, while derivatives of oxytocin, enkephalin, and melanostatin are active to a lesser degree. The selective effect on primary learning (ACTH4-7 and Leu-enkephalin) and on the consolidation and restoration of memory (vasopressin and oxytocin), and the presence of only antiamnestic properties (analog of the melanocyte-inhibiting factor) - all this suggests different mechanisms of action of these agents. Memory modulators act more strongly upon activated systems that are already prepared to receive the signal. A promising object for future study as a therapeutic antiamnestic factor is the long-term memory modulator arginine vasopressin.
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| 2863936 |
Somatostatin receptors |
10.1007/978-1-4615-7886-4_16. |
Adv Exp Med Biol |
Somatostatin receptors
Abstract
- It is now well established that the biological actions of tetradecapeptide somatostatin (somatostatin-14, S-14) are receptor-mediated. These receptors were first quantified in GH4C pituitary tumor cells using 125I-Tyr1 S-14 as radioligand which was found to exhibit high non-specific binding to membrane receptor preparations from normal tissues. Our studies have shown that 125I-Tyr11 S-14 in which the radiolabel is situated away from the N-terminus exhibits significantly lower non-specific binding and therefore is more suitable for S-14 receptor studies. In the CNS, highest concentration of S-14 receptors was found in the cerebral cortex, followed by thalamus, hypothalamus, striatum, amygdala and hippocampus while medulla-pons, cerebellum and spinal cord exhibited negligible binding. Outside the CNS membrane receptors for S-14 have been characterized in pituitary, adrenal cortex and pancreatic acini. In all these tissues a single class of high affinity binding sites for S-14 were present, the receptors in pancreatic acinar cells exhibiting significantly greater affinity for binding S-14 than in other tissues.
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| 2866500 |
The use of striatal dopaminergic supersensitivity for the evaluation of drugs with possible antidyskinetic properties |
None |
Pol J Pharmacol Pharm |
The use of striatal dopaminergic supersensitivity for the evaluation of drugs with possible antidyskinetic properties
Abstract
- An animal model of tardive dyskinesia was used for the evaluation of potential antidyskinetic properties of the neuropeptide L-Prolyl-L-Leucyl-glycinamide (PLG) and related drugs: cycloglycine-(1-amino-1-cyclopentane) carbonyl--c(CPC-Gly) and cycloalanine-(1-amino-1-cyclopentane) carbonyl--c(CPC-Ala). Dopaminergic supersensitivity was induced by repeated administration of the neuroleptic drug isofloxythepin. Isofloxythepin (5 mg/kg/day po) after the withdrawal increased Bmax of 3H-spiperone striatal binding sites, significantly decreased HVA level in the striatum and induced tolerance to the cataleptic effects challenged by perphenazine. PLG, c(CPC-Gly) and c(CPC-Ala) counteracted supersensitive responses of isofloxythepin. The use of c(CPC-Gly) and c(CPC-Ala) in the prevention of tardive dyskinesia is proposed.
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| 2866533 |
A comparison of the opioid antagonist properties of novel somatostatin analogs in vitro |
None |
Proc West Pharmacol Soc |
A comparison of the opioid antagonist properties of novel somatostatin analogs in vitro
Abstract
|
| 2867956 |
Effects of somatostatin and its analog on gastric secretion. An application of the secretagogues to gastric secretion |
10.1254/fpj.86.189. |
Nihon Yakurigaku Zasshi |
Effects of somatostatin and its analog on gastric secretion. An application of the secretagogues to gastric secretion
Abstract
- A simple technique to examine the effects of drugs on the gastric secretion response to the secretagogues without anesthesia was shown in this paper. The administration of bethanechol (1 mg/kg, s.c.), histamine (15 mg/kg, s.c.) or pentagastrin (0.25 mg/kg, i.p.) significantly increased the gastric volume and the total acid output in the pylorus-ligated rat. These responses to the secretagogues were inhibited by N-butylscopolamine, urogastrone or cimetidine dose-dependently. N-butylscopolamine (0.5 mg/kg, i.p.) inhibited the response to bethanechol but not that to pentagastrin or histamine. Cimetidine (5 mg/kg, i.p.) inhibited not only the response to histamine but also the acid response to bethanechol or pentagastrin. Urogastrone (5 mg/kg, i.p.) inhibited the response to these three secretagogues. The ratio of the total acid output to the gastric volume was also examined in each of the cases. Somatostatin (0.1 mg/kg, i.p.) inhibited the response to pentagastrin, but not that to bethanechol or histamine. On the other hand, an analogue of somatostatin (SS-1; 0.1 mg/kg, i.p.) inhibited the response to bethanechol but not that to pentagastrin or histamine.
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| 2871162 |
A sensitive high performance liquid chromatographic assay of a new metabolite of ampicillin in man |
10.1111/j.2042-7158.1986.tb04551.x. |
J Pharm Pharmacol |
A sensitive high performance liquid chromatographic assay of a new metabolite of ampicillin in man
Abstract
- A sensitive, high-performance liquid chromatographic method has been developed for the determination of piperazine-2,5-dione, a new metabolite of ampicillin, in human urine. Piperazine-2,5-dione was separated from human urine on a C18-column using phosphate buffer-methanol (pH 3.5) as eluent. Subsequently, the effluent underwent a postcolumn reaction with mercurous chloride and was then detected at 305 nm. It was found that piperazine-2,5-dione was also excreted in the urine of a volunteer dosed with ampicillin.
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| 2871546 |
Characteristics of D-Trp8-somatostatin-sensitive B50 phosphorylation |
10.1016/0196-9781(85)90434-6. |
Peptides |
Characteristics of D-Trp8-somatostatin-sensitive B50 phosphorylation
Abstract
- Inhibition of the phosphorylation of the synaptic plasma membrane (SPM) protein B50 by D-Trp8-somatostatin in vitro is time-dependent. Increasing the time of incubation of hippocampal synaptic plasma membranes with the peptide from 15 sec to 30 min prior to addition of 7.5 microM gamma-32PATP results in a complete reduction of B50 phosphorylation. Incubation of synaptic plasma membranes for 30 min in the absence of peptide does not alter basal B50 phosphorylation. Neither ACTH nor beta-endorphin produces similar effects--inhibition of B50 phosphorylation by ACTH is maximal at 15 sec and beta-endorphin produces only a small inhibition, even after 30 min. D-Trp8-somatostatin is not activating a membrane-bound protease, since maximal inhibition of B50 phosphorylation by the peptide is seen in the presence of leupeptin or bacitracin. Hippocampal synaptic plasma membranes contain protein phosphatase activity. Assays of B50 phosphorylation in synaptic plasma membranes done under conditions that favor either net phosphorylation or dephosphorylation are consistent with inhibition of protein phosphatase activity by D-Trp8-somatostatin. This evidence suggests that D-Trp8-somatostatin interacts with SPM binding sites in the hippocampus, which may alter the activity of an endogenous protein phosphatase to determine the degree of B50 phosphorylation.
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| 2872162 |
Does vasopressin sustain blood pressure in conscious spontaneously hypertensive rats? |
10.1161/01.hyp.8.6.514. |
Hypertension |
Does vasopressin sustain blood pressure in conscious spontaneously hypertensive rats?
Abstract
- To investigate the possible role of arginine vasopressin in maintaining high blood pressure of spontaneously hypertensive rats (SHR), the effect of two arginine vasopressin pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous arginine vasopressin were studied in conscious, freely moving SHR and in Wistar-Kyoto rats (WKY). Intravenous injections of either d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg, or dPTyr(Me)arginine vasopressin, 20 micrograms/kg, had no effect on mean arterial pressure or heart rate of normohydrated SHR, although both antagonists almost completely abolished the pressor response to exogenous arginine vasopressin. Furthermore, dPTyr(Me)arginine vasopressin was ineffective in eliciting a depressor response, even after 24 or 48 hours of water deprivation. During converting enzyme inhibition with SQ 20881, mean arterial pressure and heart rate remained unchanged following arginine vasopressin blockade in both normohydrated and fluid-restricted animals. alpha-Adrenergic receptor blockade reduced the blood pressure of normohydrated SHR, from 160 +/- 7 to 81 +/- 8 mm Hg. When dPTyr(Me)arginine vasopressin was given during alpha-adrenergic receptor blockade there was a small, transient fall in mean arterial pressure. The pressor responsiveness to exogenous arginine vasopressin was similar in hypertensive and normotensive rats. These results suggest that arginine vasopressin does not function as an important pressor hormone in conscious SHR.
|
| 2872176 |
Use of carboethoxysulfenyl chloride for disulfide bond formation |
10.1111/j.1399-3011.1986.tb01822.x. |
Int J Pept Protein Res |
Use of carboethoxysulfenyl chloride for disulfide bond formation
Abstract
- The use of carboethoxysulfenyl chloride for disulfide bond formation and concomitant cyclization of five peptides was investigated. Even though cyclic peptides were obtained very rapidly and in good yields when cyclization was performed in aqueous media at different pHs (4 to 7), the final crude peptides were found to contain closely related impurities which, in the case of somatostatin and pressinoic acid, were not generated by air oxidation. This observation may limit the use of carboethoxysulfenyl chloride to those cases where other methods of disulfide bond formation prove inadequate.
|
| 2872570 |
Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors |
10.1016/0024-3205(86)90574-6. |
Life Sci |
Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors
Abstract
- 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 125ICGP 23,996 (des-Ala1-,Gly2-desamino-Cys3Tyr11-dicarba3, 14-somatostatin), 3Hnaloxone or 3HDPDPE (D-Pen2-D-Pen5enkephalin) 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.
|
| 2874104 |
Effects of somatostatin and its analogue, des (Ala1, Gly2) D-Trp8, D-Asu3,14-somatostatin (SS-1), on gastric mucosal blood flow and gastric secretion |
10.1254/fpj.87.551. |
Nihon Yakurigaku Zasshi |
Effects of somatostatin and its analogue, des (Ala1, Gly2) D-Trp8, D-Asu3,14-somatostatin (SS-1), on gastric mucosal blood flow and gastric secretion
Abstract
- The inhibitory effects of somatostatin and its analogue (SS-1) on gastric mucosal blood flow (MBF) and gastric secretion were studied using bethanechol and pentagastrin as stimulants in anesthetized rats. In the present study, the inhibitory action of SS-1 was particularly investigated, regarding somatostatin as the control compound. Pretreatment with SS-1 at 1, 10, 30, or 100 micrograms/kg, i.v. (single dosing), inhibited the increase of MBF and gastric secretion stimulated by bethanechol in a dose-dependent manner. SS-1 showed no marked difference from somatostatin in terms of the degree and manner of the inhibition until 30 min after treatment. At 90 min, however, SS-1 still showed an inhibitory action, which was more prominent in gastric secretion than in MBF. Thus, SS-1 had a longer duration of action than somatostatin. Generally, SS-1 and somatostatin inhibited MBF to the same degree, whereas SS-1 inhibited gastric secretion more strongly than somatostatin. When pentagastrin was used to stimulate MBF and gastric secretion, SS-1 inhibited MBF and gastric secretion to the same degree as did somatostatin, but again, SS-1 had a longer duration of action than somatostatin.
|
| 2877871 |
Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. |
10.1002/j.1460-2075.1986.tb04528.x |
EMBO J. |
Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.
Abstract
- To identify structural characteristics of the closely related cell surface receptors for insulin and IGF-I that define their distinct physiological roles, we determined the complete primary structure of the human IGF-I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30-residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF-I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.
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| 2878649 |
Selective inhibitory effect of the analog D5-F-TrP8-D-Cys14 somatostatin on the arginine induced release of insulin, growth hormone and glucagon, in normal human beings |
None |
Arch Invest Med (Mex) |
Selective inhibitory effect of the analog D5-F-TrP8-D-Cys14 somatostatin on the arginine induced release of insulin, growth hormone and glucagon, in normal human beings
Abstract
|
| 2882015 |
Pharmacologic evaluation of a cyclic somatostatin analog with antagonist activity at mu opioid receptors in vitro |
None |
J Pharmacol Exp Ther |
Pharmacologic evaluation of a cyclic somatostatin analog with antagonist activity at mu opioid receptors in vitro
Abstract
- The cyclic somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2(CTP) was evaluated for agonist and opioid antagonist actions and receptor selectivity in two bioassays: electrically stimulated guinea pig isolated ileum (GPI) and mouse isolated vas deferens (MVD). CTP (100, 300, 1000 nM) produced concentration-dependent antagonism of the mu agonist Me-Phe3,D-Pro4morphiceptin (PL017) in both the GPI and MVD. Schild analysis of the interactions between CTP and PL017 indicated competitive antagonism between these peptides (Schild slope GPI -0.97 +/- 0.16, Schild slope MVD -1.4 +/- 0.4), and also suggested that the mu receptors in the two tissues are not different (pA2 GPI 7.1 +/- 0.17, pA2 MVD 6.9 +/- 0.16). The effects of the delta selective agonist D-Pen2,D-Pen5enkephalin in the MVD were not antagonized by CTP. Likewise, in the GPI, CTP did not antagonize the kappa agonist (trans-3-4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenea cetamine (U50, 488H). In comparison, naloxone antagonized both PL017 and U50,488H in the GPI, as well as D-Pen2,D-Pen5enkephalin and PL017 in the MVD. In the MVD, CTP also exerted weak somatostatin-like actions (35% maximal inhibition) that could not be demonstrated in somatostatin-tolerant tissues. It also showed inhibitory actions at very high concentrations (3000 and 10,000 nM) that were blocked by both naloxone and the delta antagonist N,N-diallyl-Tyr-AIB-AIB-Phe-Leu-OH (ICI 174,864). ICI 174,864 antagonized D-Pen2,D-Pen5enkephalin in the MVD, but did not affect PL017. These results indicate that CTP is a selective mu receptor antagonist in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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