Muscarinic regulation of phospholipase A2 and iodide fluxes in FRTL-5 thyroid cells.
FRTL-5 thyroid cells express a muscarinic receptor which inhibits the phospholipase C activity in a pirenzepine-insensitive manner. We here report that the cholinergic agonist carbachol decreases in these cells the steady-state iodide content, an effect correlated with the iodination of thyroglobulin and with thyroid hormone formation. Several signal pathways may be involved in this phenomenon since carbachol in addition to inhibiting phospholipase C, increased the arachidonic acid release and modified the adenylyl cyclase activity. In FRTL-5 cells, arachidonic acid is released via the direct stimulation of phospholipase A2 by a pirenzepine-sensitive muscarinic receptor coupled to a GTP binding protein sensitive to pertussis toxin. Regarding adenylyl cyclase, carbachol potentiated the thyrotropin-induced stimulation of the enzyme, whereas it did not affect the basal levels of cAMP. In vitro binding studies revealed the presence of two muscarinic binding sites. To summarize, the analysis of signal pathways and of in vitro binding sites indicates a complex muscarinic regulation of thyroid function, which includes the modulation of iodide fluxes.
Di Girolamo
M
M
Laboratory of Cellular and Molecular Endocrinology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy.
D'Arcangelo
D
D
Bizzarri
C
C
Corda
D
D
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D007454:Iodides / Q000378:metabolism*; D009116:Muscarine / Q000378:metabolism*; D019832:N-Methylscopolamine; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
D001095:Arachidonic Acids; D007454:Iodides; D012602:Scopolamine Derivatives; D016718:Arachidonic Acid; D009116:Muscarine; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D019832:N-Methylscopolamine