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Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells

Nature volume 315, pages 752–755 (1985)Cite this article

Abstract

It is now established that a key step in the action of calcium-mobilizing agonists is stimulation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to 1,2-diacylglycerol and inositol 1,4,5-1 ris phosphate (InsP3)1,2. The latter substance acts as a second messenger, controlling the release of calcium from intracellular stores (see ref. 3 for review). The bifurcating nature of the signalling system is exemplified by the fact that the other product of PtdIns(4,5)P2 hydrolysis, 1,2-diacylglycerol, can alter cellular function by activating protein kinase C, the cellular target for several tumour-promoting agents such as the phorbol esters4,5. In various tissues, including GH3 pituitary tumour cells, a synergistic interaction between calcium ions and protein kinase C underlies agonist-induced changes in cell activity4,6–10. The data presented here suggest that when GH3 cells are stimulated by thyrotropin-releasing hormone (TRH), an agonist inducing PtdIns(4,5)P2 hydrolysis11–14, the two limbs of the inositol lipid signalling system interact to control free cytosolic calcium levels ([Ca2+]i). At low levels of TRH receptor occupancy, [Ca2+]i)increases rapidly, then declines relatively slowly. As receptor occupancy increases, the calcium signal becomes more short-lived due to the appearance of a second, inhibitory, component. This latter component, which is enhanced when [Ca2+]i) is elevated by high potassium depolarization, is mimicked by active phorbol esters and by bacterial phospholipase C. It seems likely that protein kinase C subserves a negative feedback role in agonist-induced calcium mobilization.

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  1. Department of Pharmacology, University of Glasgow, Glasgow, G12 8QQ, UK

    Alan H. Drummond

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Drummond, A. Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells. Nature 315, 752–755 (1985). https://doi.org/10.1038/315752a0

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