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Stimulatory activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors.

Wang, W (author)
Guo, G (author)
Tang, J (author)
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Li, J (author)
Zhao, R (author)
Hjalmarson, Åke, 1937 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
Fu, Michael, 1963 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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 (creator_code:org_t)
2000
2000
English.
In: Chinese medical journal. - 0366-6999. ; 113:10, s. 867-71
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • OBJECTIVE: To study the activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors on cAMP production and inward calcium currents (Ica) in guinea pig ventricular myocytes. A comparison was also made with those of a muscarinic receptor agonist. METHODS: cAMP content was determined by radioimmunoassay and the Ica in guinea pig single ventricular cells were recorded by the whole-cell patch clamp technique. RESULTS: Both the muscarinic receptor agonist, carbachol (Carb 10 mumol/L), and anti-peptide antibodies (Abs 100 nmol/L) could decrease basal cAMP levels (by 46.9% +/- 4.2% and 60.2% +/- 4.6%, respectively) and basal Ica. Both Carb (10 mumol/L) and Abs (100 nmol/L) could also inhibit the isoprenaline-induced (Iso 0.8 mumol/L) increases in cAMP production (from 108.2 +/- 7.0 to 88.4 +/- 7.2 pmol/mg.protein/min for Carb and 88.6 +/- 5.1 pmol/mg.protein/min for Abs, respectively) and the increases in Ica. The muscarinic receptor antagonist atropine (Atr) was able to prevent these effects of Carb and Abs. CONCLUSIONS: Anti-peptide antibodies against an epitope located in the second extracellular loop of human M2 muscarinic receptors, similar to muscarinic receptor agonist, could decrease the basal Ica and beta-receptor agonist stimulated increase of Ica by decreasing the basal and beta-receptor agonist stimulated increase of cAMP production, and therefore could have an effect on their target receptor. These results further suggest that autoimmunity may participate in the pathogenesis of human cardiomyopathy and the second extracellular loop of human M2 muscarinic receptor could be the main immunodominant region.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Amino Acid Sequence
Animals
Antibodies
immunology
Atropine
pharmacology
Calcium
metabolism
Carbachol
pharmacology
Cyclic AMP
biosynthesis
Female
Guinea Pigs
Humans
Male
Molecular Sequence Data
Peptide Fragments
immunology
Receptor
Muscarinic M2
Receptors
Muscarinic
immunology

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor
Wang, W
Guo, G
Tang, J
Li, J
Zhao, R
Hjalmarson, Åke, ...
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Fu, Michael, 196 ...
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Microbiology in ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Cell and Molecul ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Physiology
Articles in the publication
Chinese medical ...
By the university
University of Gothenburg

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