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 between purinoceptor and endothelin (ET) receptor, or glutamate receptor. The treatments of adenosine triphosphate (ATP), ET-1, and glutamate induced the increase of intracellular calcium level in the astrocytes. In repetitive additions of ATP to astrocytes, the second application of ATP exhibited comparable amplitude of calcium response, but the stimulation with ATP completely blocked subsequent ET-1- or glutamate-evoked calcium responses showing complete heterologous desensitization. In contrast, ET-1 and glutamate failed to desensitize the response elicited by ATP. Preincubation with sphingosine, a protein kinase C (PKC) inhibitor, reversed the ATP-induced desensitization of ET-1- and glutamate-evoked calcium responses. Taken together, these results demonstrate the resistance of purinoceptor to homologous desensitization, and unidirectional desensitization between ATP and other receptors such as ET and glutamate receptors, suggesting a dominant role of purinoceptor in modulating calcium signal of astrocytes.
Cho
Y J
YJ
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Lee
S Y
SY
Kim
Y S
YS
Lee
E J
EJ
Seo
M S
MS
Yeon
G
G
Lee
K H
KH
Lee
K J
KJ
Jo
Y K
YK
Rha
H K
HK
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D019332:Endothelin-1; D017466:Receptors, Endothelin; D017470:Receptors, Glutamate; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium