Adenosine triphosphate-induced heterologous desensitization of endothelin-1-and glutamate-evoked calcium increases in cultured rat cortical astrocytes

In rat cortical astrocytes, we investigated the occurrence of cross-talks b etween purinoceptor and endothelin (ET) receptor, or glutamate receptor. Th e treatments of adenosine triphosphate (ATP), ET-1, and glutamate induced t he increase of intracellular calcium level in the astrocytes. In repetitive additions of ATP to astrocytes, the second application of ATP exhibited co mparable amplitude of calcium response, but the stimulation with ATP comple tely blocked subsequent ET-1- or glutamate-evoked calcium responses showing complete heterologous desensitization. In contrast, ET-1 and glutamate fai led to desensitize the response elicited by ATP. Preincubation with sphingo sine, a protein kinase C (PKC) inhibitor, reversed the ATP-induced desensit ization of ET-1- and glutamate-evoked calcium responses. Taken together, th ese results demonstrate the resistance of purinoceptor to homologous desens itization, and unidirectional desensitization between ATP and other recepto rs such as ET and glutamate receptors, suggesting a dominant role of purino ceptor in modulating calcium signal of astrocytes. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.