Cardiac beta-adrenoceptor changes in monocrotaline-treated rats: differences between membrane preparations from whole ventricles and isolated ventricular cardiomyocytes.
In monocrotaline (MCT)-treated rats the beta-adrenoceptor-G-protein-adenylyl cyclase system-determined in crude membrane preparations from whole ventricular tissue-was desensitized not only in right (RV) but also in left ventricles (LV). This study aimed to assess the specific contribution of cardiomyocytes to these beta-adrenoceptor changes. Six-week-old male Wistar rats were treated with 60 mg/kg body weight MCT intraperitoneally; within 4-6 weeks, rats developed marked RV hypertrophy. Cardiomyocytes were isolated from RVs and LVs. In RV cardiomyocytes of MCT-treated rats, beta-adrenoceptor density was significantly reduced whereas it was unaltered in LV cardiomyocytes. Reduction of RV cardiomyocyte beta-adrenoceptors was due to a selective beta(1)-adrenoceptor reduction. Isoprenaline (100 microM)-induced cAMP increase was significantly reduced in RV but not in LV cardiomyocytes of MCT-treated rats. G protein-coupled receptor kinase activity was increased in RV but not in LV cardiomyocytes. alpha(1)-Adrenoceptor density and noradrenaline-induced increase in inositol phosphate formation were significantly reduced only in RV but not in LV cardiomyocytes from MCT-treated rats. It is concluded that in cardiomyocytes of MCT-treated rats, cardiac beta-adrenoceptors and alpha -adrenoceptors are chamber-specifically desensitized only in the RV. Thus, changes in cardiac beta-adrenoceptors determined in membrane preparations from whole tissue homogenates do not correctly reflect changes occurring in cardiomyocytes.
Leineweber
Kirsten
K
Institute of Pharmacology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany.
Seyfarth
Torsten
T
Abraham
Getu
G
Gerbershagen
Hans-Peter
HP
Heinroth-Hoffmann
Ingrid
I
Pönicke
Klaus
K
Brodde
Otto-Erich
OE
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D016686:Monocrotaline; D009638:Norepinephrine