Inhibition of alpha 1-adrenoceptor-mediated inositol phosphate accumulation in cultured cardiac myocytes by cyclic AMP-generating compounds.
Exclusive stimulation of the alpha 1-adrenoceptor in cultured cardiac myocytes led to a time-dependent increase of multiple inositol phosphate isomers. However, under physiological conditions, alpha 1-adrenergic stimulation is accompanied by beta-adrenergic stimulation as noradrenaline is a ligand for both receptors. Thus, the aim of our study was to investigate the cross-talk between the alpha 1- and the beta-adrenoceptor on the post-receptor level. When both the alpha 1- and the beta-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 alpha 1-adrenoceptor for 30 s. In contrast, after 15 min the inhibitory effect of simultaneous beta-stimulation as well as of forskolin pre-treatment upon the alpha 1-mediated inositol phosphate response was abolished, although the concentration of cAMP was still elevated. These data suggest that beta-adrenoceptor- and forskolin-induced cAMP production or a cAMP-activated subsequent signal have a short-term, transient, inhibitory effect on alpha 1-adrenoceptor-mediated inositol phosphate response.
Institute of Biochemistry and Food Chemistry, Department of Biochemistry, Hamburg, Germany.
A H
AH
Guse
I
I
Berg
G
G
Gercken
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP