Tetrodotoxin-sensitive and -resistant effects of veratridine on the noradrenergic neurone of the rat vas deferens.
The veratridine-induced release of 3H-noradrenaline from noradrenergic neurones was examined in the isolated vas deferens of either untreated or reserpine plus pargyline-pretreated rats. The rat vas deferens, whose catechol O-methyltransferase was inhibited, was first incubated with 0.4 mumol/l 3H-(-)noradrenaline (30 min) and then washed repeatedly with amine-free solution. After 120 min (i.e., well after the efflux of tritium from the tissue had reached a steady level and was predominantly of neuronal origin), washout was continued in the presence of veratridine for further 10-15 min. In vasa deferentia of untreated rats, veratridine (1-100 mumol/l) caused a concentration-dependent increase in the efflux of tritium. At high concentrations of the drug (30 or 100 mumol/l), this increase in efflux was peak-like during the first 3 min ("peak response") and then fell to a plateau ("plateau response"). In the presence of veratridine, unchanged 3H-noradrenaline accounted for about 75% of the tritium efflux (the rest being represented by deaminated 3H-catechol metabolites). The "peak response" to veratridine (100 mumol/l) was abolished by tetrodotoxin (TTX; 1 mumol/l) or the absence of external Ca2+. Cocaine (10 mumol/l) affected neither the "peak response" as such nor the contribution by 3H-noradrenaline to the efflux of tritium during that response. Hence, the "peak response" was due to exocytotic release of 3H-noradrenaline from the neurone. The "plateau response" to veratridine (100 mumol/l) was unaffected by the absence of external Ca2+, largely resistant to TTX (1 mumol/l) and moderately reduced by cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004351:Drug Resistance; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D014316:Tritium; D013779:Tetrodotoxin; D014701:Veratridine; D012110:Reserpine; D010293:Pargyline; D014702:Veratrine; D003042:Cocaine; D009638:Norepinephrine