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Cholinergic control of cyclic nucleotide metabolism in human thyroid cells

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Abstract

In the presence of Ro 20-1724, a selective inhibitor of cyclic nucleotide phosphodiesterase, carbamylcholine increases cAMP and cGMP levels in human thyroid cells in primary culture. The increase of cAMP exhibited at concentrations of carbamylcholine between 10 fM and 10 pM, is dose- and time-dependent, it is maximum after 30 min and is abolished after 60 min. At higher carbamylcholine concentration (10 μM), cAMP increases rapidly, becoming maximum after 15 min, but returns to unstimulated values after 30 min. The increase of cGMP is also dose- dependent (0.1 nM–10 μM); it reaqqches the maximum after 30 min and returns to unstimulated values after 120 min. A significant increase of phosphodiesterase activity is observed at 10 μM carbamylcholine. Atropine, a muscarinic receptor antagonist, blocks carbamylcholine effects on both cAMP and cGMP production without affecting the thyrotropin-induced cAMP accumulation. Hexamethonium, a nicotinic receptor antagonist does not affect the cholinergic effects. In the presence of Ro 20-1724, 10 μM carbamylcholine significantly inhibits the effect of thyrotropin on cAMP production, while the combined addition of low doses of carbamylcholine and thyrotropin (0.1 nM and 10 pM, respectively) results in ah additive effect on cAMP levels. Inhibition of thyrotropin activity on cAMP production, similar to that exerted by 10 μM carbamylcholine is produced by increasing free intracellular calcium; this inhibition is relieved by using a calmodulin-sensitive phosphodiesterase inhibitor, M and B 22948 at 50 μM dose. High concentrations (10 μM) of carbamylcholine increase the adenylate cyclase activity, without any significant effect on the thyrotropin-induced activation of the enzyme. The data presented in this study show, for the first time, that in primary cultures of human thyroid cells, cAMP production is increased by a cholinergic agent acting through muscarinic receptors. Cholinergic activity can either potentiate or inhibit thyrotropin action depending on the concentration of neurotransmitter available. Accelerated catabolism by the activation of the calmonodulin-sensitive phosphodiesterase can explain the inhibitory effect of carbamylcholine on the cellular accumulation of cAMP.

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Authors and Affiliations

  1. Clinica Medica III, University of Firenze, 50100, Firenze, Italy

    M. L. Brandi, C. M. Rotella, A. Tanini & R. Toccafondi

  2. Centro di Endocrinologia ed Oncologia Sperimentale del CNR, and Dipartimento di Biologia e Patologia Cellulare e Molecolare “L. Califano”, University of Napoli, 80100, Napoli, Italy

    S. M. Aloj

  3. Laboratory of Biochemistry and Metabolism, NIDDK, Building 10, Room 9B-13, NIH, Bethesda, Maryland, 20892, USA

    S. M. Aloj

Authors
  1. M. L. Brandi
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  2. C. M. Rotella
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  3. A. Tanini
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  4. R. Toccafondi
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  5. S. M. Aloj
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Brandi, M.L., Rotella, C.M., Tanini, A. et al. Cholinergic control of cyclic nucleotide metabolism in human thyroid cells. J Endocrinol Invest 10, 451–458 (1987). https://doi.org/10.1007/BF03348169

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  • DOI: https://doi.org/10.1007/BF03348169

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