Effect of voltage-sensitive calcium channel antagonists on the release of 5-hydroxytryptamine from rat hippocampus in vivo.
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 microM), 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, omega-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 omega-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.
Pullar
I A
IA
Lilly Research Centre Ltd., Eli Lilly and Company, Windlesham, Surrey, England, U.K.
Findlay
J D
JD
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D012701:Serotonin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium