Article date: November 1989
By: Richard A. Keith, Thomas J. Mangano, Andre I. Salama in Volume 98, Issue 3, pages 767-772
The role of voltage‐sensitive calcium channels (VSCC) in N‐methyl‐D‐aspartate (NMDA)‐ and kainic acid (KA)‐evoked neurotransmitter release from rat cortical and hippocampal brain slices was evaluated by determining the effects of ω‐conotoxin GVIA, an inhibitor of neuronal L‐ and N‐type VSCC, and PN 200–110, a selective inhibitor of L‐type VSCC.
Selective antagonists of the NMDA receptor ionophore complex, Mg2+, CPP and MK‐801, inhibited NMDA‐ but not KA‐evoked release of [3H]‐noradrenaline from hippocampal and cortical brain slices. This suggests that cortical and hippocampal receptors are similar and that NMDA and KA act at distinct excitatory amino acid receptor subtypes.
[3H]‐noradrenaline release induced by both NMDA and KA was similarly inhibited (approximately 30%) by ω‐conotoxin GVIA. In contrast, PN 200–110 had no significant effect, although there was a tendency towards inhibition.
The results suggest that although NMDA‐ and KA‐receptors are pharmacologically distinct, the N‐type, but not the L‐type, VSCC plays a small but significant role in neurotransmitter release induced by both NMDA and KA. It remains to be determined whether the N‐type VSCC are involved in the physiological and/or pathological manifestations of excitatory amino acid receptor stimulation.
The role of voltage‐sensitive calcium channels (VSCC) in N‐methyl‐D‐aspartate (NMDA)‐ and kainic acid (KA)‐evoked neurotransmitter release from rat cortical and hippocampal brain slices was evaluated by determining the effects of ω‐conotoxin GVIA, an inhibitor of neuronal L‐ and N‐type VSCC, and PN 200–110, a selective inhibitor of L‐type VSCC.
Selective antagonists of the NMDA receptor ionophore complex, Mg2+, CPP and MK‐801, inhibited NMDA‐ but not KA‐evoked release of [3H]‐noradrenaline from hippocampal and cortical brain slices. This suggests that cortical and hippocampal receptors are similar and that NMDA and KA act at distinct excitatory amino acid receptor subtypes.
[3H]‐noradrenaline release induced by both NMDA and KA was similarly inhibited (approximately 30%) by ω‐conotoxin GVIA. In contrast, PN 200–110 had no significant effect, although there was a tendency towards inhibition.
The results suggest that although NMDA‐ and KA‐receptors are pharmacologically distinct, the N‐type, but not the L‐type, VSCC plays a small but significant role in neurotransmitter release induced by both NMDA and KA. It remains to be determined whether the N‐type VSCC are involved in the physiological and/or pathological manifestations of excitatory amino acid receptor stimulation.
DOI: 10.1111/j.1476-5381.1989.tb14604.x
View this article