Abstract:
:To investigate the structure-activity relationships for potent and selective action of enkephalins at the delta-opioid receptors, two newly synthesized analogues, [Cys(O2NH2)2,Leu5]enkephalin and [Cys(O2NH2)2, Met5] enkephalin and the hexapeptide [D-Ala2,Leu5]enkephalyl-Arg (dalargin) were tested and compared with [Leu5]enkephalin and [Met5]enkephalin, for their effectiveness to inhibit electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective delta-opioid receptors) and the guinea pig ileum (mu- and kappa-opioid receptors). The mouse vas deferens assays included evaluation of the effects of opioid agonists on the first, purinergic, and the second, adrenergic, components of electrically evoked biphasic responses (10 Hz and 20 Hz) and on ATP- or noradrenaline-evoked, tetrodotoxin-resistant responses. The opioids tested inhibited in a similar manner: (i) the purinergic and the adrenergic components of the electrically evoked contractions; and (ii) the ATP- and noradrenaline-induced postjunctional responses of the mouse vas deferens. Extremely low IC50 values (of 2-5 orders) were found for [Cys(O2NH2)2,Leu5] enkephalin, whose relative potency was between 239 and 1316 times higher than that of [Leu5]enkephalin. The order of potency for the other peptides in this tissue was: [Cys(O2NH2)2,Met5]enkephalin > [Leu5]enkephalin > dalargin > [Met5]enkephalin. The highest IC50 values in the guinea pig ileum assays, indicating the lowest affinity for mu-/kappa-opioid receptors, were obtained for the cysteine sulfonamide analogues, while dalargin showed a potency four times higher than that of [Met5]enkephalin. The order of potency in this tissue was: dalargin > [Met5]enkephalin > [Leu5]enkephalin > [Cys(O2NH2)2,Met5]enkephalin > [Cys(O2NH2)2,Leu5]enkephalin. The ratio, IC50 in guinea pig ileum: IC50 in mouse vas deferens, indicating selectivity of the respective peptide for delta-opioid receptors, was extremely high for [Cys(O2NH2)2,Leu5]enkephalin and especially for the adrenergic component of the responses. This ratio for [Cys(O2NH2)2,Met5]enkephalin was higher than the ratios for dalargin, [Leu5]enkephalin and [Met5]enkephalin, which were about 3 orders of magnitude lower. The results suggest that incorporation of hydrophilic Cys(O2NH2) in the enkephalin molecule greatly increases the potency and selectivity of the analogues at delta-opioid receptors, while both D-Ala2 substitution and lengthening of the peptide chain by Arg6 in the molecule of [Leu5]enkephalin decrease them.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Pencheva N,Bocheva A,Dimitrov E,Ivancheva C,Radomirov Rdoi
10.1016/0014-2999(96)00083-0subject
Has Abstractpub_date
1996-05-23 00:00:00pages
99-108issue
1-3eissn
0014-2999issn
1879-0712pii
0014-2999(96)00083-0journal_volume
304pub_type
杂志文章abstract::Glutamine is the most abundant amino acid in the bloodstream. It is important in nucleotide synthesis, is anti-catabolic, has anti-oxidant properties via metabolism to glutathione, may enhance immune responsiveness and possesses immunoregulatory functions. Moreover, it reduces atrophy of intestinal mucosa in animals o...
journal_title:European journal of pharmacology
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doi:10.1016/j.ejphar.2011.02.008
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abstract::The pharmacological properties of two angiotensin II analogues containing carboranylalanine (Car) are reported. Sar-Arg-Val-Tyr-Val-His-Pro-Car is a weak partial agonist showing 15% intrinsic activity and a very long lasting action, specific for the angiotensin II receptor of the rabbit aorta. Sar-Arg-Val-Car-Val-His-...
journal_title:European journal of pharmacology
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doi:10.1016/0014-2999(80)90458-6
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journal_title:European journal of pharmacology
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doi:10.1016/s0014-2999(97)01424-6
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90053-1
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abstract::Pleurisy was induced in rats by an intrapleural injection of 0.5 ml of 1% kaolin. The exudation of plasma into the pleural cavity showed two peaks at 20 min and 3-5 h after the kaolin injection. The volume of the pleural fluid increased gradually up to 5 h. The effects of treatment with mepyramine, methysergide, capto...
journal_title:European journal of pharmacology
pub_type: 杂志文章
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abstract::Cardiovascular and behavioral responses induced by intravenous administration of the serotonin (5-HT)1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in conscious normotensive rats either after a single administration, after repeated subcutaneous treatments (1 mg/kg daily for 3 day...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90140-l
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journal_title:European journal of pharmacology
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abstract::A series of potent bombesin antagonists based on the reduced C-terminal peptide bond modification which in the past resulted in the first really potent antagonists are compared for effects on bombesin-stimulated amylase release from and binding to rat and guinea pig pancreatic acini. It was found that the original mem...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94109-b
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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doi:10.1016/j.ejphar.2013.01.054
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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abstract::The suitability of various neurokinin-2 (NK2) receptor agonists and routes of administration to elicit on-demand voiding of the bladder and bowel, as future therapy for individuals with spinal cord injury, was examined using a rat model. The current study examined the feasibility of alternative routes of administratio...
journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90346-2
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90381-q
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90324-8
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abstract::The effects of the two enantiomers of the antidepressant nomifensine on catecholamine uptake were investigated using rat brain synaptosomes. According to the results from in vitro and ex vivo/in vitro studies, the inhibitory activity on catecholamine uptake resides entirely in the (+)-form of nomifensine. Further stud...
journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90617-6
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.07.054
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00045-4
更新日期:1998-04-10 00:00:00