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Effect of metoprolo...
Effect of metoprolol on activity of beta-adrenoceptor coupled to guanine nucleotide binding regulatory proteins in adriamycin-induced cardiotoxicity.
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- Fu, Michael, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergh, Claes-Håkan, 1951 (författare)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Wallenberglaboratoriet,Cardiovascular Institute,Wallenberg Laboratory
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Hoebeke, Johan (författare)
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- Liang, Qi-Ming (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Sjögren, Klas-Göran (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Waagstein, Finn, 1938 (författare)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Wallenberglaboratoriet,Cardiovascular Institute,Wallenberg Laboratory
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- Hjalmarson, Åke, 1937 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Hjärt-kärlinstitutionen,Wallenberg Laboratory,Cardiovascular Institute
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(creator_code:org_t)
- 1991
- 1991
- Engelska.
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Ingår i: Basic research in cardiology. - 0300-8428. ; 86:2, s. 117-26
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- Prevention of cardiotoxicity without interfering with the therapeutic efficacy of adriamycin is a very crucial question. We have investigated the activity of beta-adrenoceptor coupled to guanine nucleotide binding regulatory proteins (G-proteins) and Ca(2+)-ATPase activity in experimental adriamycin-induced cardiotoxicity and the influence of metoprolol treatment on these variables. Adriamycin was administered to rats intravenously as a single dose of 6 mg/kg, and metoprol was continuously given by means of implanted osmotic pumps. beta-Adrenoceptor characteristics were measured by radioligand-binding experiments and by basal and stimulated adenylyl cyclase activity. Northern blot and dot blot analysis was used to quantify G-protein mRNA. It was shown that adriamycin did not induce any change in the total beta-adrenoceptor density, nor did the high affinity agonist binding to beta-adrenoceptor change. Adriamycin did not induce any alteration in the amount of mRNA encoding for stimulatory (Gs) or inhibitory (Gi) G-proteins. Also, basal and stimulated adenylyl cyclase activities were identical in the different experimental groups. In contrast, the Ca(2+)-ATPase was shown to increase in adriamycin-treated rats compared to control rats (45 +/- 3.8 versus 23 +/- 1.2 mumol Pi/mg/h, P less than .01). Metoprolol was shown to normalize this increase (29 +/- 2.1 mumol Pi/mg/h). Thus, it may be concluded that in experimental adriamycin-induced cardiotoxicity, despite Ca(2+)-overloading, the beta-adrenoceptor-G protein-adenylyl cyclase system remains intact. Metoprolol seems to prevent Ca(2+)-overloading independently of the beta-adrenoceptors studied here.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Adenylate Cyclase
- metabolism
- Animals
- Blotting
- Northern
- Calcium-Transporting ATPases
- metabolism
- Doxorubicin
- GTP-Binding Proteins
- genetics
- metabolism
- Heart Diseases
- chemically induced
- metabolism
- Iodine Radioisotopes
- diagnostic use
- Iodocyanopindolol
- Kinetics
- Male
- Membranes
- metabolism
- Metoprolol
- pharmacology
- Nucleic Acid Hybridization
- Pindolol
- analogs & derivatives
- diagnostic use
- RNA
- Messenger
- metabolism
- Radioligand Assay
- Rats
- Rats
- Inbred Strains
- Receptors
- Adrenergic
- beta
- drug effects
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Fu, Michael, 196 ...
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Bergh, Claes-Håk ...
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Hoebeke, Johan
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Liang, Qi-Ming
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Sjögren, Klas-Gö ...
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Waagstein, Finn, ...
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Hjalmarson, Åke, ...
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Göteborgs universitet