Abstract:
:The subcellular distribution of cardiac muscarinic receptors was defined in canine ventricular myocardium, and receptors were solubilized from subcellular fractions enriched in muscarinic receptor content. The subcellular location of muscarinic receptors in cardiac tissue was determined by measurement of the distribution of [3H](+/-)quinuclidinyl benzilate-binding activity in particulate fractions isolated from canine ventricular myocardium. Based upon excellent correlation between [3H](+/-)quinuclidinyl benzilate binding and activity of the sarcolemmal Na+,K+-ATPase throughout the subcellular fractions, muscarinic receptors appeared to be localized to sarcolemma in canine ventricular myocardium. Therefore, membrane fractions enriched in sarcolemma were used as a source of cardiac muscarinic receptors for solubilization. Treatment of membrane vesicle fractions with digitonin (0.6%) resulted in solubilization of [3H](+/-)quinuclidinyl benzilate-binding activity with an extraction yield of 25-35%. Criteria of pharmacological specificity and stereospecificity established the identity of the solubilized binding activity of muscarinic receptors. Solubilization of muscarinic receptors was documented by demonstration of hydrodynamic behavior consistent with molecularly dispersed material. Upon glycerol gradient centrifugation, digitonin-solubilized muscarinic receptors from cardiac tissue sedimented with an apparent sedimentation coefficient of 9S. Pharmacological characterization of the digitonin-solubilized receptors revealed 8- to 39-fold reductions in affinities for muscarinic antagonists compared to the affinities exhibited by receptors in the membrane-bound state. Substantially greater reductions in agonist affinities (reduction of at least 700-fold for all agonists studied) suggested selective loss of ability of the digitonin-solubilized receptors to exhibit high affinity agonist interactions. In contrast to membrane-bound receptors, digitonin-solubilized receptors also demonstrated a loss of guanine nucleotide regulation, as well as steep agonist:radioligand competition curves with slope factors of 1.0, suggesting a homogeneous population of agonist-binding sites. Interpreted within the context of a model of state interconversion for membrane-bound receptors, the results suggested that either muscarinic receptors of a single state were selectively solubilized, or that solubilization induced conversion of all receptors to a single low affinity state, possibly by removal of constituents necessary for assumption of a high affinity agonist conformation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Manalan AS,Werth DK,Jones LR,Watanabe AMdoi
10.1161/01.res.52.6.664subject
Has Abstractpub_date
1983-06-01 00:00:00pages
664-76issue
6eissn
0009-7330issn
1524-4571journal_volume
52pub_type
杂志文章abstract:RATIONALE:One of the physiological mechanisms by which the heart adapts to a rise in blood pressure is by augmenting myocyte stretch-mediated intracellular calcium, with a subsequent increase in contractility. This slow force response was first described over a century ago and has long been considered compensatory, but...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.256743
更新日期:2011-12-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.3.780
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1161/01.res.69.6.1608
更新日期:1991-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.RES.0000233315.38086.bc
更新日期:2006-07-21 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.1.193
更新日期:1993-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150755
更新日期:2007-12-07 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.70.4.633
更新日期:1992-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-03-16 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000124979.46214.E3
更新日期:2004-04-16 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.2.294
更新日期:1975-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.4.669
更新日期:1996-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.63.6.1020
更新日期:1988-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.5.481
更新日期:1998-09-07 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.6.864
更新日期:1985-12-01 00:00:00
abstract::The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantit...
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pub_type: 杂志文章
doi:10.1161/01.res.62.1.155
更新日期:1988-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-07-17 00:00:00
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更新日期:2007-08-03 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-01-07 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.3.462
更新日期:1994-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-08-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2002-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2005-08-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.844
更新日期:1994-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.6.998
更新日期:1996-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.761
更新日期:1975-06-01 00:00:00
abstract::The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to ele...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2002-07-26 00:00:00