INHIBITION OF ALPHA-1-ADRENOCEPTOR-MEDIATED INOSITOL PHOSPHATE ACCUMULATION IN CULTURED CARDIAC MYOCYTES BY CYCLIC AMP-GENERATING COMPOUNDS

Exclusive stimulation of the α1-adrenoceptor in cultured cardiac myocytes led to a time-dependent increase of multiple inositol phosphate isomers. However, under physiological conditions, α1-adrenergic stimulation is accompanied by β-adrenergic stimulation as noradrenaline is a ligand for both receptors. Thus, the aim of our study was to investigate the cross-talk between the α1- and the β-adrenoceptor on the post-receptor level. When both the α1- and the β-adrenoceptor were stimulated with noradrenaline for 30 s, a diminished increase in all inositol phosphates and a concomitant increase in cAMP was observed. Similar results were obtained by pre-incubation of the myocytes with forskolin for 2 min and subsequent stimulation of the α1-adrenoceptor for 30 s. In contrast, after 15 min the inhibitory effect of simultaneous β-stimulation as well as of forskolin pre-treatment upon the α1-mediated inositol phosphate response was abolished, although the concentration of cAMP was still elevated. These data suggest that β-adrenoceptor- and forskolin-induced cAMP production or a cAMP-activated subsequent signal have a short-term, transient, inhibitory effect on α1-adrenoceptor-mediated inositol phosphate response. © 1991.