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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001613,
umls-concept:C0007776,
umls-concept:C0018787,
umls-concept:C0022655,
umls-concept:C0031978,
umls-concept:C0034440,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0205145,
umls-concept:C0228174,
umls-concept:C0231491,
umls-concept:C0449560,
umls-concept:C0599668,
umls-concept:C0851285,
umls-concept:C1167622,
umls-concept:C1880022
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pubmed:issue |
2
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pubmed:dateCreated |
1986-6-23
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pubmed:abstractText |
Studies show [3H]PZ identified selectively a subpopulation of muscarinic binding sites compared to classical antagonists like (-)-[3H]QNB in many central and peripheral tissues. We characterized the binding and regulation of selected antagonists to high-affinity [3H]PZ (putative M1) and low-affinity PZ (putative M2) sites in rat cerebral cortex (predominantly M1) and heart (predominantly M2). Saturation isotherms of [3H]PZ and (-)-[3H]QNB were performed under various conditions. Guanyl-5'-yl-imidodiphosphate (30 microM) showed little effect on Kd (dissociation constant) or total binding capacity (total receptor density) values. Higher ionic strength buffers yielded lower affinity values for [3H]PZ and (-)-[3H]QNB. Kinetic studies confirmed high affinity Kd values seen in steady-state assays. We conducted inhibition studies of selected muscarinic antagonists including the reportedly cardioselective (putative M2) drug, AF-DX 116 (11-[(2-(diethylamino)methyl-1-piperidinyl)-acetyl]-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one], the reportedly M1 selective compound, PZ, and the classical antagonist (-)QNB, using [3H]PZ and (-)-[3H]QNB-labeled cerebral cortical and cardiac homogenates. Assays were done with and without guanyl-5'-yl-imidophosphate at 25 degrees C in 10 mM Na-K-phosphate, 50 mM Na-K-phosphate and modified Krebs-phosphate buffer. Studies showed antagonists generally had higher affinity in 10 mM Na-K-phosphate buffer, were insensitive to guanyl-5'-yl imidodiphosphate and had Hill values (nH) nearly equal to one. Cardiac PZ/[3H]QNB curves were steep.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepinones,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Ethylmaleimide,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylyl Imidodiphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Parasympatholytics,
http://linkedlifedata.com/resource/pubmed/chemical/Pirenzepine,
http://linkedlifedata.com/resource/pubmed/chemical/Quinuclidines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinuclidinyl Benzilate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
237
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
419-27
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3754581-Animals,
pubmed-meshheading:3754581-Benzodiazepinones,
pubmed-meshheading:3754581-Buffers,
pubmed-meshheading:3754581-Cerebral Cortex,
pubmed-meshheading:3754581-Ethylmaleimide,
pubmed-meshheading:3754581-Guanylyl Imidodiphosphate,
pubmed-meshheading:3754581-Kinetics,
pubmed-meshheading:3754581-Male,
pubmed-meshheading:3754581-Myocardium,
pubmed-meshheading:3754581-Parasympatholytics,
pubmed-meshheading:3754581-Pirenzepine,
pubmed-meshheading:3754581-Quinuclidines,
pubmed-meshheading:3754581-Quinuclidinyl Benzilate,
pubmed-meshheading:3754581-Rats,
pubmed-meshheading:3754581-Rats, Inbred Strains,
pubmed-meshheading:3754581-Receptors, Muscarinic,
pubmed-meshheading:3754581-Tritium
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pubmed:year |
1986
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pubmed:articleTitle |
[3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites. II. Characterization and regulation of antagonist binding to putative muscarinic subtypes.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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