Norepinephrine, unlike ATP, induces all-or-none increase in cytosolic calcium in thyroid cells. The role of inositol-trisphosphate-sensitive stores and calcium channels.
The mechanism of action of norepinephrine and ATP has been analyzed in single FRTL5 cells (a normal thyroid cell line), loaded with the fluorescent Ca2+ probe Fura2. ATP increased the cytosolic Ca2+ in an apparently concentration-dependent manner with a maximal effect at 10 microM (413 +/- 26% over basal levels of 135 +/- 7 nM). In contrast, the norepinephrine-induced increase (198 +/- 5% over basal) was concentration independent in individual cells, the minimal effective concentration being 1 nM. However, the number of cells responding to norepinephrine was concentration dependent. The ATP-induced Ca2+ rise was biphasic, consisting of a rapid rise (2-4 s, 252 +/- 15%), resembling the effect of norepinephrine, followed by a slower and longer component, which reached a plateau in 0.5-2 min. The second component appeared to be related to the opening of a channel, since it required extracellular Ca2+ and was abolished by SC38249, an inhibitor of the second-messenger-operated and voltage-operated channels. Moreover, it was inhibited by 4 beta-phorbol 12-myristate 13-acetate, suggesting that protein kinase C might be involved in the modulation of this Ca2+ channel.
Bizzarri
C
C
Istituto di Richerche Farmacologiche, Mario Negri, Consorzio Mario Negri Sud, Laboratory of Cellular and Molecular Endocrinology, Santa Maria Imbaro, Italy.
Corda
D
D
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D016257:Fura-2 / Q000737:chemistry; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D007093:Imidazoles; D007295:Inositol Phosphates; C053318:1-(2,3-bis((4-methoxyphenyl)methoxy)propyl)-1H-imidazole; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013930:Thromboxane-A Synthase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine