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Volume 270, Number 28, Issue of July 14, pp. 16630-16637, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.

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Heterologous Desensitization of Opioid-stimulated Ca Increase by Bradykinin or ATP in NG108-15 Cells

Sheau-Huei Chueh , Shu-Ling Song , Tsui-Ying Liu

Leucine-enkephalin (Leu-EK) dose-dependently elicited an increase in cytosolic Ca concentration ([Ca]) with an EC of 1.2 µM via the phosphoinositide cascade in NG108-15 cells. Chronic treatment of cells with [D-Ala,D-Leu]enkephalin caused time-dependent homologous desensitization. In the presence of extracellular Ca, ATP as well as bradykinin stimulated significantly higher increases in inositol 1,4,5-trisphosphate (IP) generation than did Leu-EK; however, the magnitude of intracellular Ca pools increased after ATP stimulation, whereas bradykinin depleted intracellular pools. Hence, cells lost their [Ca] response to Leu-EK if bradykinin was first added to induce a [Ca] increase, whereas the response was unchanged if Leu-EK was added after addition of ATP. When Leu-EK was added simultaneously with bradykinin or ATP, an additive response was observed in IP generation; however, the rise in [Ca] reached the same level as that induced by bradykinin or ATP alone. In the absence of extracellular Ca in which the replenishment of intracellular pools was not possible, ATP displayed an inhibitory effect similar to that of bradykinin on the Leu-EK-induced [Ca] increase. Prior treatment of cells with Leu-EK slightly heterologously desensitized the action of bradykinin, but had no effect on the ATP response. Our results suggest that a shared intracellular Ca pool is sensitive to the opioid, bradykinin and P-purinoceptor agonists; however, a defined pool of phosphatidylinositol 4,5-bisphosphate or a specific phospholipase C is responsible for each receptor.

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