The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens.
After loading of the incubated rat vas deferens with 0.2 mumol/l 3H-noradrenaline (followed by 100 min of wash-out with amine-free solution), the efflux of endogenous and exogenous compounds was determined by HPLC with electrochemical detection and by column chromatography with scintillation counting. Two different types of heterogeneity of labelling were found. The first one is due to the preferential labelling of varicosities close to the surface of the tissue, the second one to the preferential labelling of vesicles close to the surface of loaded varicosities. As diffusion distances within the tissue and within varicosities are then longer for endogenous than for exogenous amine and metabolites, the composition of spontaneous efflux of exogenous compounds differed from that for endogenous compounds. Because of preferential neuronal and vesicular re-uptake of endogenous noradrenaline, the percentage contribution by noradrenaline to overall efflux was: endogenous less than exogenous. While 3H-DOPEG was the predominant exogenous metabolite, DOPEG and MOPEG equally contributed to the "endogenous" efflux. Desipramine abolished the consequences of the first heterogeneity of labelling, i.e., it increased the efflux more for endogenous than for exogenous noradrenaline; moreover it decreased the efflux of 3H-DOPEG, but increased that of 3H-MOPEG. The reserpine-like compound Ro 4-1284, on the other hand, abolished the consequences of the second type of heterogeneity; it reduced the specific activity of "total efflux" (i.e., of the sum of noradrenaline + DOPEG + MOPEG) to the specific activity of the tissue noradrenaline. The degree of heterogeneity of labelling was reduced after inhibition of monoamine oxidase and also when the tissues were loaded with 2 or 20 mumol/l 3H-noradrenaline. It is proposed that the various "compartments" and "pools" of noradrenaline described in the literature reflect the two heterogeneities described here.
Schömig
E
E
Institut für Pharmakologie und Toxikologie der Universität Würzburg, Federal Republic of Germany.
Schönfeld
C L
CL
Halbrügge
T
T
Graefe
K H
KH
Trendelenburg
U
U
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014439:Tyramine / Q000494:pharmacology; D014649:Vas Deferens / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; D008734:Methoxyhydroxyphenylglycol; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine