Temporal integration of alpha 1-adrenergic responses in BC3H-1 muscle cells. Regulation of glycogen phosphorylase activity.
Regulation of Ca2+-dependent glycogen phosphorylase activity by alpha 1-adrenergic and H1-histamine receptors has been examined in BC3H-1 muscle cells. Stimulation by either norepinephrine or histamine elevates the phosphorylase activity ratio within 5 s from a resting value of 0.37 +/- 0.03 to maximal values of 0.8-0.9. Phosphorylase activation by alpha-adrenergic agonists is sustained over 20-30 min of agonist exposure, whereas histamine exposure only transiently activates phosphorylase during the initial 5 min of stimulation. The initial activation of phosphorylase by either receptor is not attenuated by treated cells with Ca2+-deficient and [ethylenebis(oxyethylenenitrilo)]tetraacetic acid-supplemented buffer, whereas the response to sustained adrenergic stimulation depends largely, but not totally, upon extracellular Ca2+. The involvement of protein kinase C in agonist responses was tested by treating cells with phorbol 12-myristate 13-acetate. Phorbol 12-myristate 13-acetate inhibits receptor-mediated mobilization of intracellular Ca2+ (IC50 = 3.6 nM) yet activates phosphorylase independently of agonist. Phorbol 12-myristate 13-acetate has no effect on cellular 45Ca2+ fluxes in the absence of agonist. Thus, the two receptors coordinately regulate intracellular signaling through Ca2+- and protein kinase C-mediated pathways. alpha 1-Adrenergic receptors elicit sustained phosphorylase activation whereas H1-histaminergic receptors desensitize.
Toranji
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Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Brown
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D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D006005:Phosphorylases / Q000096:biosynthesis / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D011942:Receptors, Adrenergic, alpha; D011968:Receptors, Histamine; D000001:Calcimycin; D006005:Phosphorylases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium