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European Heart Journal 1991 12(Supplement F):139-142; doi:10.1093/eurheartj/12.suppl_F.139
Copyright © 1991 by the European Society of Cardiology.
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© 1991 The European Society of Cardiology

Regulation of adenylyl cyclase by noradrenaline and tumour necrosis factor {alpha} in rat cardiomyocytes

C. Reithmann, P. Gierschik*, K. H. Jakobs* and K. Werdan

Medizinische Klinik I, Universität München, Klinikum GroBhadern D-8000 München 70, Marchioninistr. 15
* Pharmakologisches Institut, Universität Heidelberg Germany

Correspondence: Christopher Reithmann, Medizinijche Klinik I, Universität München, Klinikum GroBhadem, D-8000 München 70, Marchioninistr. 15, Germany

The regulation of adenylyl cyclase components and of adenylyl cyclase activity by noradrenaline and tumour necrosis factor {alpha} (TNF{alpha}) was studied in rat cardiomyocytes. Long-term treatment of rat cardiomyocytes in the presence of noradrenaline leads, in addition to a down-regulation of β1-adrenoceptors, to an increase in the level of inhibitory G protein {alpha}-subunits and to a heterologous descnsitization of adenylyl cyclase stimulation. Similar to the noradrenaline exposure, incubation of the cardiomyocytes in the presence of the cytokine TNF{alpha} (10 U. ml–1) also increases the level of G1{alpha} proteins. However, in contrast to the noradrenaline treatment, which apparently induces a selective up-regulation of G1{alpha}, the TNF{alpha} exposure also increases the level or activity of other components of adenylyl cyclase, such as the level of membrane β36-subunits of G proteins and, most likely, the level of the {alpha}-subunits of the stimulatory G protein (Gs{alpha}) and the activity of adenylyl cyclase catalytic subunit. While noradrenaline treatment desensitizes receptor-dependent and independent adenylyl cyclase activity, treatment of the cells with TNF{alpha} induces a sensia'zation of adenylyl cyclase stimulation.

The data indicate that only a selective increase in the level of inhibitory G protein a subunits decreases adenylyl cyclase activity. The hypersensitivity of adenylyl cyclase induced by TNF{alpha} exposure may be due to concomitant alterations of other components of the adenylyl cyclase signal transduction system.

Key Words: Adenylyl cyclase • G proteins • noradrenaline • tumour necrosis factor {alpha}


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