Calcium dependence of beta-adrenoceptor mediated cyclic AMP accumulation in human lymphocytes.
In intact human lymphocytes, cyclic AMP accumulation in response to isoproterenol was inhibited by 5 mM EDTA, by deletion of calcium ions from the medium and by 1 mM lanthanum chloride, but not by 1 microM verapamil or by 10 microM nifedipine. A23187 caused a modest increase in cyclic AMP content. Exposure of lymphocytes to 5 microM 1-isoproterenol desensitized the cells to subsequent beta-adrenergic stimulation, reducing cyclic AMP accumulation. With higher concentrations of 1-isoproterenol (50 microM), receptor density was reduced as well. None of the above agents attenuated losses in agonist-stimulated cyclic AMP accumulation induced by treatment with 5 microM isoproterenol for 90 min. These data suggest that calcium ions, both those present in the extracellular medium and those bound to the plasma membrane, are required for isoproterenol-stimulation of adenylate cyclase. In addition, it appears that neither the presence of extracellular calcium ions nor full activation of adenylate cyclase are required for desensitization.
Borst
S
S
Division of Clinical Pharmacology, UCLA School of Medicine 90024.
Conolly
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; C028521:lanthanum chloride; D000001:Calcimycin; D007811:Lanthanum; D004492:Edetic Acid; D014700:Verapamil; D000242:Cyclic AMP; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine