Effect of Voltage‐Sensitive Calcium Channel Antagonists on the Release of 5‐Hydroxytryptamine from Rat Hippocampus In Vivo

Publisher Website
Google Scholar
Abstract
The effect of calcium channel antagonists on the release of 5‐hydroxytryptamine from the hippocampus of the chloral hydrate‐anaesthetised rat was studied using the technique of intracerebral microdialysis. As the basal concentration of 5‐hydroxytryptamine was close to the limit of detection of the HPLC method (8 fmol), the 5‐hydroxytryptamine reuptake inhibitor, fluoxetine (10 μM], was included in the perfusion fluid. The l‐type voltage‐sensitive calcium channel antagonists, PN200‐110, diltiazem, and verapamil, all passed through the dialysis membrane, giving a recovery of 20‐30%. The N‐type voltage‐sensitive calcium channel antagonist, ω‐conotoxin, penetrated less readily (12% recovery). The dihydropyridine, PN200‐110, adhered to the probe, resulting in an effective concentration at the membrane 30% of that in the perfusion fluid. The concentration of 5‐hydroxytryptamine in the dialysate samples was reduced by 60% in the absence of calcium. The L channel antagonists had little effect on the release of 5‐hydroxytryptamine, which was inhibited, in a dose‐dependent manner, to a maximum of 40% by w‐conotoxin. It is concluded that, under physiological conditions, the release of 5‐hydroxytryptamine from the rat hippocampus is dependent on the entry of calcium through N‐type voltage‐sensitive calcium channels, although another calcium channel may also be involved.