Inhibition of ATP-induced Ca2+ influx by corticosterone in dorsal root ganglion neurons.
In addition to the classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomic effects on neurons. In the present study, the effect of corticosterone (CORT) on ATP-induced Ca(2+) mobilization in cultured dorsal root ganglion (DRG) neurons were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator that could monitor real-time alterations of intracellular calcium concentration ([Ca(2+)]i). ATP, an algesic agent, caused [Ca(2+)]i increase in DRG neurons by activation of P2X receptor. Pretreatment with CORT (1 nM-1 microM for 5 min) inhibited ATP-induced [Ca(2+)]i increase in DRG neurons. The rapid inhibition of ATP-induced Ca(2+) response by CORT was concentration-dependent, reversible and could be blocked by glucocorticoid receptor antagonist RU38486 (10 microM). Furthermore, the inhibitory effect of CORT was abolished by protein kinase A inhibitor H89 (10 microM), but was not influenced by protein kinase C inhibitor Chelerythrine chloride (10 microM). On the other hand, membrane-impermeable bovine serum albumin-conjugated corticosterone had no effect on ATP-induced [Ca(2+)]i transients. These observations suggest that a nongenomic pathways may be involved in the effect of CORT on ATP-induced [Ca(2+)]i transients in cultured DRG neurons.
Liu
Xiaohong
X
Department of Neurobiology, College of Medicine, Third Military Medical University, 30 Gaotanyan Street, 400038, Shapingba District, Chongqing, People's Republic of China.
Zeng
Junwei
J
Zhao
Yandong
Y
Xiao
Zhi
Z
Fang
Chuanqing
C
Ruan
Huaizhen
H
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D007546:Isoquinolines; D011965:Receptors, Glucocorticoid; D013449:Sulfonamides; C439264:bovine serum albumin-corticosterone conjugate; D012710:Serum Albumin, Bovine; D015735:Mifepristone; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium; D003345:Corticosterone