Intra- and extraneuronal metabolism of 5-hydroxytryptamine in the isolated saphenous vein of the dog.
The uptake and metabolism of 3H-5-hydroxytryptamine (5-HT) in the isolated saphenous vein of the dog was studied, as well as the sensitivity to 5-HT and its termination of action (as determined by oil immersion experiments). After exposure of the vein to 0.23 mumol/1 5-HT for 30 min, about one half of the 5-HT removed was accumulated in the tissue, the other half appearing in the form of metabolites. Cocaine, chlorimipramine or denervation reduced the accumulation, but not the metabolism, of 5-HT; hydrocortisone reduced both accumulation and metabolism. Hydrocortisone plus cocaine (or phenoxybenzamine alone) caused a greater reduction of accumulation and metabolism than hydrocortisone or cocaine alone. Pargyline caused an increase in accumulation and virtually abolished metabolism; amezinium also abolished metabolism, but reduced accumulation (the same effects as caused by cocaine plus pargyline). Cocaine (12 mumol/l) caused supersensitivity to 5-HT and a prolongation of the half-time for relaxation in oil; hydrocortisone (40 mumol/l) had no effect on sensitivity, but prolonged somewhat the half-time for relaxation in oil, showing supra-additive effects with cocaine. 5-HT, taken up into adrenergic nerve terminals, was released by electrical stimulation; no appreciable reduction in fractional release occurred during repeated stimulations. Exposure to cocaine prior to incubation with 5-HT prevented the neuronal uptake of 5-HT. Compartmental analysis, done with the help of washout curves of strips pretreated with pargyline and loaded with 3H-5-HT, shows that 3H-5-HT distributed into 3 compartments plus a bound fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009121:Muscle Denervation; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012501:Saphenous Vein / Q000294:innervation / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D003042:Cocaine; D006854:Hydrocortisone