Veratridine-induced outward transport of 3H-noradrenaline from adrenergic nerves of the rat vas deferens.
1. The neuronal release by 100 mumol/l veratridine of preloaded 3H-noradrenaline was studied in the rat vas deferens, the MAO, COMT and vesicular uptake of which were inhibited. To prevent any exocytotic release of the 3H-amine, all solutions were calcium-free. Veratridine induced an early and a late peak of tritium efflux. The early peak was abolished by the presence of 1 mumol/l desipramine, the late peak was abolished by 1 mumol/l tetrodotoxin (administered subsequently to the first peak). The administration of veratridine plus 1 mmol/l ouabain resulted in only the early peak of efflux. 2. The peak response to veratridine plus ouabain was increased by a very early administration of veratridine plus ouabain (after 40 min of wash-out instead of the usual 130 min) (i.e., when the relative size of the axoplasmic distribution compartment was increased). However, very high axoplasmic 3H-noradrenaline levels (after loading with 37 instead of the usual 0.2 mumol/l) reduced the height of the peak (when expressed as a FRL). 3. Substantially similar responses to veratridine plus ouabain were obtained after loading with 3H-noradrenaline, 3H-adrenaline or 3H-dopamine. 4. As the second peak of veratridine-induced release is ouabain-sensitive, it appears to be caused by exhaustion of neuronal ATP stores; this, in turn, raises the intravesicular pH and induces efflux of 3H-noradrenaline from the vesicles into the axoplasm. The first peak, on the other hand, represents outward transport of 3H-noradrenaline from the axoplasmic compartment. Evidently, a pronounced vesicular distribution of 3H-noradrenaline takes place even after inhibition by reserpine of the vesicular uptake. 5. In preparations with intact vesicular uptake (MAO and COMT inhibited) a plateau-response was obtained; in the presence of 10 mumol/l Ro 4-2184 (a reserpine-like compound) a peak response was restored after loading with 0.2 mumol/l 3H-noradrenaline, less so after loading with 37 mumol/l. 6. It is confirmed that veratridine (plus ouabain) exerts a reserpine-like effect when applied to tissues with intact vesicular uptake and intact MAO.
Bönisch
H
H
Pharmakologisches Institut der Universität Würzburg, Federal Republic of Germany.
Trendelenburg
U
U
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D065098:Catechol O-Methyltransferase Inhibitors; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology; D014649:Vas Deferens / Q000294:innervation; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D065098:Catechol O-Methyltransferase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D013566:Sympathomimetics; D010042:Ouabain; D014701:Veratridine; D014702:Veratrine; D009638:Norepinephrine