Mechanism of (-)clausenamide induced calcium transient in primary culture of rat cortical neurons.
(-)clausenamide is a compound isolated from Clausena lansium (lour) Skeel with nootropic effects. At the present study, we investigated the clausenamide induced Ca2+ signaling in primary cultures of rat cortical neurons by using laser confocal microscopy. The mean amplitude of (-)clausenamide (1 microM) induced Ca2+ transient was similar in extracellular solution with or without calcium; and (-)clausenamide failed to trigger calcium transient after treatment with endoplasmic reticulum Ca2+ pumps inhibitor BHQ to exhaust intracellular Ca2+ stores. This result suggested that the primary source of (-)clausenamide induced Ca2+ transient was from internal stores. Application of IP3 receptor inhibitor MgCl2 and PLC-gamma inhibitor U73122 suppressed (-)clausenamide induced Ca2+ transient, suggesting that the major source of (-)clausenamide induced Ca2+ transient was from IP3 receptor pathway. We also found that mitochondria were involved in (-)clausenamide triggered Ca2+ transient. The distinctive spatial and temporal characteristic of (-)clausenamide induced Ca2+ transient may play an important role in its action.
Tang
Kang
K
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Zhang
Jun-Tian
JT
D000814:Aniline Compounds; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007769:Lactams / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D027821:Rutaceae / Q000737:chemistry; D013237:Stereoisomerism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014966:Xanthenes
D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007769:Lactams; D017705:Lignans; D014966:Xanthenes; C053048:clausenamide; C059715:Fluo-3; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D008274:Magnesium