Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons.
OBJECTIVE
To investigate whether agmatine could selectively block a given type of the voltage-gated calcium channels (VGCC) and whether related receptors are involved in the blocking effect of agmatine on VGCC.


METHODS
The whole-cell patch recording technique was performed to record VGCC currents in the cultured neonatal rat hippocampal neurons.


RESULTS
Verapamil (100 micromol/L), a selective blocker of L-type calcium channel, significantly inhibited VGCC current by 80 %+/- 7 %. Agmatine (100 micromol/L) could further depress the remained currents by 25 %+/-6 %. The alpha 2-adrenoceptor antagonist yohimbine (10 micromol/L) and the I2 imidazoline receptor antagonist idazoxon (10 and 40 micromol/L) had no significant effect on VGCC currents when used respectively. When the mixture of yohimbine and agmatine was applied, VGCC currents were still depressed remarkably. However, the blocking effect of agmatine was decreased by 29 %+/- 8 % in the presence of idazoxon (10 micromol/L). The effect of idazoxon did not increase at a higher concentration (40 micromol/L).


CONCLUSIONS
Agmatine could block the L- and other types of VGCC currents in the cultured rat hippocampal neurons. Blocking effect of agmatine on VGCC was partially related to I2 imidazoline receptor and had no relationship with alpha 2-adrenoceptors.
Zheng
Jian-quan
JQ
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. jqzh@yahoo.com
Weng
Xie-chuan
XC
Gai
Xiao-dan
XD
Li
Jin
J
Xiao
Wen-bin
WB
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015016:Yohimbine; D000376:Agmatine; D014700:Verapamil