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Properties of G-pro...
Properties of G-protein modulated receptor-adenylyl cyclase system in myocardium of spontaneously hypertensive rats treated with adriamycin.
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- Fu, Michael, 1963 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Matoba, M (author)
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- Liang, Qi-Ming (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Sjögren, Klas-Göran (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Hjalmarson, Åke, 1937 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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(creator_code:org_t)
- 1994
- 1994
- English.
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In: International journal of cardiology. - 0167-5273. ; 44:1, s. 9-18
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Abstract
Subject headings
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- Properties of the receptor--G protein--adenylyl cyclase system were studied in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) treated with adriamycin (ADR, 1 mg/kg per week) for 12 weeks. An identical dosing schedule caused a significantly greater decline in body weight gain and a marked elevation of plasma norepinephrine level in SHR than in WKY. A significant increase in the messenger RNA encoding Gi-alpha 2 was found in SHR+ADR group. The activity of the adenylyl cyclase stimulated by guanyliminodiphosphate [Gpp(NH)p] was decreased by 49% in SHR and 73% in SHR+ADR. However, stimulated activities of adenylyl cyclase by both sodium fluoride and forskolin remained unchanged. Functional level of stimulatory G-protein (Gs) as measured by reconstitution assay in sarcolemmal membrane was unaltered among different groups. Furthermore, the density of beta-adrenoceptor was significantly decreased without change of its affinity. Muscarinic receptors exhibited a three-site affinity distribution in SHR+ADR whereas other groups displayed only two-site affinity distribution. These results suggest that SHR exhibited a depressed myocardial adenylyl cyclase signaling system which may not be due to the functional uncoupling of beta-adrenoceptors from Gs but to the increased inhibitory G-protein (Gi) activity as demonstrated by the increased mRNA of Gi-alpha 2, increased inhibition of Gpp(NH)p-mediated adenylyl cyclase and the super high affinity for carbachol of the muscarinic receptors. Decreased beta-adrenoceptor density and functional alteration of Gi might be regarded as the predisposing factors for the increased susceptibility of myocardium of SHR to ADR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Adenylate Cyclase
- physiology
- Animals
- Doxorubicin
- pharmacology
- GTP-Binding Proteins
- genetics
- physiology
- Heart
- physiopathology
- Hypertension
- physiopathology
- Male
- Myocardium
- chemistry
- Norepinephrine
- blood
- RNA
- Messenger
- analysis
- Rats
- Rats
- Inbred SHR
- Rats
- Inbred WKY
- Receptors
- Adrenergic
- beta
- physiology
- Receptors
- Muscarinic
- analysis
- Sarcolemma
- chemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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