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Effect of Voltage‐Sensitive Calcium Channel Antagonists on the Release of 5‐Hydroxytryptamine from Rat Hippocampus In Vivo
Author(s) -
Pullar Ian A.,
Findlay Jeremy D.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09405.x
Subject(s) - chemistry , calcium channel , voltage dependent calcium channel , microdialysis , calcium , verapamil , dihydropyridine , diltiazem , pharmacology , nitrendipine , chloral hydrate , isradipine , biophysics , biochemistry , medicine , extracellular , biology , organic chemistry
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 μ M ], 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.