Ograniczanie wyników

Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 22

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

Wyszukiwano:
w słowach kluczowych:  opioid peptide
help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
Conformational space of a novel cyclic enkephalin analogue, cyclo(Nε, Nε'-carbonyl-D-Lys2,Lys5) enkephalinamide, was exhaustively examined. A large number of conformations was selected and clustered into families on the basis of their structure and energy. For representative conformations ROESY spectra were generated and their linear combination was fitted to the spectra measured in water and Me2-SO-d6. This procedure yielded an ensemble of most populated conformations of the peptide in the two solvents.
To evaluate the role of aromatic amino-acids residues, four analogues of theu-selec­tive opioid peptide agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) containing the amphi­philic, a,a-disubstituted amino acid (R)- or (S)-a-hydroxymethyltyrosine (HmTyr) in position 1 and (R)- or (S)-a-hydroxymethylphenylalanine (Hm3Phe) in position 3 of the peptide sequence were synthesized. Only the [(R)- HmPhe3)]DALDA analogue dis­played full agonistic activity in both the guinea pig ileum and the mouse vas deferens assays and turned out to be a δ receptor-selective opioid agonist.
Limitations on the use of animals for biological experiments has forced a search for alternative simpler organisms for testing the biological activity of organic com­pounds. The aim of this research was to use Tetrahymena termophila for testing the opioid activity of pep­tide, -casomorphin-7, isolated from cheese. Three kinds of test were used: 1) test for in­hi­bition of protozoa mobility, 2) trap test, and 3) phagocytose test. The results for the trap test suggests that it can be used to determine the presence of harmful substances occurring in food. Determination of the opioid properties using the phagocytose test showed that morphine inhibits the phagocytose process of Tetrahymena termophila. -casomorphin-7 had smaller inhibitory effect on ph­ago­cy­to­sis than mor­phine. it can be said that our results and literature prove the possibility of using protozoa Tet­rahy­mena termophila for studies of antinutritional sub­stances and opioids in raw and food products.
A study of the effect of the tetrazole moiety, a cis-amide bond surrogate, on the Cu(II) coordinating properties of oligopeptides is reported. Insertion of the tetrazole moiety Ψ[CN4] into the peptide sequence of [D-Ala2]deltorphin I changes considerably the coordination ability of the peptide. Potentiometric and spectroscopic results show that if the tetrazole moiety is in a suitable position in the peptide chain, i.e. It follows the second residue, a stable CuL species involving 3N coordination is formed in the physiological pH range. The tetrazole Ψ[CN4] ring provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a bent peptide backbone. The peptide conformation changes achieved by Cu(II) coordination may be essential for the binding of tetrazole deltorphins at opiate receptors.
The dermorphin-derived cyclic tetrapeptide analogues H-Tyr-C[D-Cys-Phe-Cys]NH2 and H-Tyr-C[D-Cys-Phe-D-Cys]NH2 are opioid agonists at the µ and δ receptor. To enhance the metabolic stability of these peptides, we replaced the disulfide bridge with a bis-methylene moiety. This was achieved by solid-phase synthesis of the linear precursor peptide containing allylglycine residues in place of the Cys residues, followed by ring-closing metathesis. In the case of the peptide with L-configuration in the 4-position both the cis and the trans isomer of the resulting olefinic peptides were formed, whereas the cis isomer only was obtained with the peptide having the D-configuration in position 4. Catalytic hydrogenation yielded the saturated -CH2-CH2- bridged peptides. In comparison with the cystine-containing parent peptides, all olefinic peptides showed significantly reduced µ and δ agonist potencies in the guinea pig ileum and mouse vas deferens assays. The -CH2-CH2-bridged peptide with L-configuration in the 4-position was equipotent with its cystine-containing parent in both assays, whereas the bis-methylene analogue with D-configuration in position 4 was 10-27-fold less potent compared to its parent. The effect of the disulfide replacements with the -CH=CH- and ‑CH2-CH2- moieties on the conformational behavior of these peptides was examined by theoretical conformational analysis which provided plausible explanations in terms of structural parameters for the observed changes in opioid activity.
Dansylated analogues of the potent and selective u opioid peptide agonist [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine) were pre­pared either by substitution of Nε-dansyl-a,β-diaminopropionic acid or Nε-dansyl- lysine for Lys4 , or by attachment of a dansyl group to the C-terminal carboxamide function via a linker. All three analogues displayed high u agonist potency in vitro and the C-terminally dansylated one retained significant u receptor selectivity. The three analogues showed interesting differences in their fluorescence emission maxima and quantum yields, indicating that the dansyl group in two of them was engaged in intramolecular hydrophobic interactions. These dansylated [Dmt1]DALDA analogues represent valuable tools for binding studies, cellular uptake and intracellular distribution studies, and tissue distribution studies.
It is generally accepted that classical opioids exert their antinociceptive effect mainly when binding to opioid receptors located in the central nervous system. However, a growing body of evidence points to the relevance of peripheral opioid receptors in periphery pathology, including cancer. A cancer is very often the cause of pain resulting from peripheral metastasis. The peripheral component of antinociception induced by a dimeric enkephalin analog – biphalin showing limited blood-brainbarrier permeability may prove important in cancer pain therapy. An additional advantage of biphalin is a possibility to treat pain symptoms with reduction of side-effects – a result of the central action of some other opioid analgesics, e.g. morphine. We examined the peripheral and central analgesic effect of biphalin in a murine skin cancer pain model developed by an intraplantar inoculation of B16T0 melanoma cells. Animals developed robust thermal hypersensitivity in the tumor-bearing paw compared to PBS-injected individuals. Biphalin produced stronger analgesia in the tumor-bearing paw than morphine upon a comparable central effect. Our results suggest that biphalin analgesia manifested in the periphery is linked to a less effective transport through the bloodbrain barrier. We speculate that the centrally effective dose of biphalin equipotent to morphine simultaneously produces analgesia via peripheral opioid receptors. Thus, biphalin may become useful in cancer pain treatment as an alternative drug executing a local as well as a central analgesic response with limited undesirable side-effects.
Conscious rats were given i. p. polyethylene glycol (PEG) or dextran injections to compare their efficacy in inducing moderate hypovolaemia. Dextran was found unsuitable, producing large variability in the the plasma vasopressin (A VP) concentrations. Putative neurotransmitters involved in the A VP response to hypovolaemia and in basal release were examined using opioid, and ß-adrenoceptor and dopamine receptor-blocking agents. A dose of PEG was chosen to produce a decrease in blood volume of approx 14.5% giving plasma AVP concentrations of 19.0±4.6 pmol/1. Naloxone and phenoxy- benzamine failed to influence AVP release under both hypovolaemic and basal conditions. Prazosin also failed to influence the AVP response. In contrast propranolol elevated the plasma AVP concentrations in both conditions. Haloperidol enhanced basal AVP release but did not influence release during hypovolaemia. Guanethidine pretreatment partially blocked the response to hypovolaemia, but did not affect basal plasma AVP. Thus it appears that aminergic pathways have an inhibitory influence on AVP release under hypovolaemic and basal conditions. However, endogenous opioids do not appear to contribute significantly to the hypovolaemic response.
Opioid peptides are the most effective drugs in controlling pain; their action is elicited by binding to specific membrane receptors. The gastrointestinal tract represents, after the nervous system, the site in which the opioid receptors are expressed at high levels. The opioid agonist morphine has a significant inhibitory effect on intestinal motility, this action is blocked by naloxone an opioid antagonist mainly active at mu and kappa receptors. In this study the presence of mu opioid receptor on rabbit jejunum was investigated by western blot. The effects of beta-endorphin, the endogenous opioid peptide with the highest affinity to the mu opioid receptor and those of naloxone on spontaneous rabbit jejunum contractions were evaluated. Beta-endorphin (10-6M) showed a relaxant effect on jejunum contractility while naloxone showed a dual effect inducing an increase of spontaneous contractility at low concentrations (10-6M, 10-7M, 10-8M) and a decrease when high concentrations (10-3M, 10-4M, 10-5M) were utilized. The obtained results demonstrate that mu opioid receptor is expressed in rabbit jejunum and suggest that this receptor may be involved in mediating the effects of both opioid agonist and antagonist on jejunum contractions.
New analogues of deltorphin I (DT I), in which the phenylalanine residue in position 3 is substituted with amphiphilic a,a-disubstituted amino acid enantiomers, (R) and (S)-a-hydroxymethylnaphtylalanine, were synthesized and tested for u and δ opioid re­ceptor affinity and selectivity. Although both analogues have lower affinity to δ recep­tors than DT I, they both expressed specificity to δ receptors.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.