Effect of concomitant beta-adrenoceptor stimulation on alpha 1-adrenoceptor-mediated increase of inositol-1,4,5-trisphosphate mass in adult rat cardiomyocytes.
The aim of the present study was to investigate the accumulation of inositol-1,4,5-trisphosphate (IP3) in isolated adult rat ventricular cardiomyocytes after alpha 1- and beta-adrenoceptor stimulation, separate and in combination, in order to elucidate a possible influence of concomitant beta-adrenoceptor stimulation on the alpha 1-adrenoceptor stimulated response. IP3 was measured by a radioligand binding assay based on an (1,4,5)IP3-specific binding protein from bovine adrenal cortex. The basal IP3 content was 4.06 +/- 0.31 pmol/mg protein (N = 56). alpha 1-Adrenoceptor stimulation resulted in a rapid increase in the IP3 level, which reached a plateau, 50-80% above basal level, at 10-30 sec. The plateau lasted at least up to 120 sec., while at 300 sec. there was no significant difference between control values and values after alpha 1-adrenoceptor stimulation. Li+ did not affect either the basal IP3 level, or the magnitude or time course of alpha 1-adrenoceptor-stimulated IP3 accumulation. Combined adrenoceptor stimulation gave a similar response as separate alpha 1-adrenoceptor stimulation, whereas there was no significant change in the IP3 level after beta-adrenoceptor stimulation. No inhibitory influence of simultaneous beta-adrenoceptor stimulation on the alpha 1-adrenoceptor-stimulated increase of IP3 mass was revealed.
Viko
H
H
Department of Pharmacology, University of Oslo, Norway.
Sandnes
D
D
Skomedal
T
T
Osnes
J B
JB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D015544:Inositol 1,4,5-Trisphosphate; D009638:Norepinephrine