8813590

Source:http://linkedlifedata.com/resource/pubmed/id/8813590

Download in:

Switch to

Custom View

Named Graph Language Inference

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0010654, umls-concept:C0014298, umls-concept:C0059306, umls-concept:C0140057, umls-concept:C0243071
pubmed:issue	1-3
pubmed:dateCreated	1997-2-12
pubmed:abstractText	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.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/1254354
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Leucine-2-Alanine, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Methionine, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalins, http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, delta, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, kappa, http://linkedlifedata.com/resource/pubmed/chemical/enkephalin-Leu, Ala(2)-Arg(6)-, http://linkedlifedata.com/resource/pubmed/chemical/enkephalin-Leu, Cys(O2NH2)(2)-, http://linkedlifedata.com/resource/pubmed/chemical/enkephalin-Met, Cys(O2NH2)(2)-
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	0014-2999
pubmed:author	pubmed-author:BochevaAA, pubmed-author:DimitrowDD, pubmed-author:IvanchevaCC, pubmed-author:PenchevaNN, pubmed-author:RadomirovRR
pubmed:issnType	Print
pubmed:day	23
pubmed:volume	304
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	99-108
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:8813590-Adenosine Triphosphate, pubmed-meshheading:8813590-Animals, pubmed-meshheading:8813590-Dose-Response Relationship, Drug, pubmed-meshheading:8813590-Electric Stimulation, pubmed-meshheading:8813590-Enkephalin, Leucine, pubmed-meshheading:8813590-Enkephalin, Leucine-2-Alanine, pubmed-meshheading:8813590-Enkephalin, Methionine, pubmed-meshheading:8813590-Enkephalins, pubmed-meshheading:8813590-Guinea Pigs, pubmed-meshheading:8813590-Ileum, pubmed-meshheading:8813590-Male, pubmed-meshheading:8813590-Mice, pubmed-meshheading:8813590-Muscle, Smooth, pubmed-meshheading:8813590-Muscle Contraction, pubmed-meshheading:8813590-Norepinephrine, pubmed-meshheading:8813590-Receptors, Opioid, delta, pubmed-meshheading:8813590-Receptors, Opioid, kappa, pubmed-meshheading:8813590-Structure-Activity Relationship, pubmed-meshheading:8813590-Vas Deferens
pubmed:year	1996
pubmed:articleTitle	[Cys(O2NH2)2]enkephalin analogues and dalargin: selectivity for delta-opioid receptors.
pubmed:affiliation	Institute of Physiology, Bulgarian Academy of Sciences, Sofia. iph@bgcict.bitnet; or: nevena@iph.bio.acad.bg
pubmed:publicationType	Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't