Copyright © 1991 by the European Society of Cardiology.
© 1991 The European Society of Cardiology
Regulation of adenylyl cyclase by noradrenaline and tumour necrosis factor
in rat cardiomyocytes
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
(TNF
) 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
-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
(10 U. ml–1) also increases the level of G1
proteins. However, in contrast to the noradrenaline treatment, which apparently induces a selective up-regulation of G1
, the TNF
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
-subunits of the stimulatory G protein (Gs
) 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
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
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 