The role played by the extraneuronal system in the disposition of noradrenaline and adrenaline in vessels

Abstract

The role played by extraneuronal sites in the disposition of noradrenaline and adrenaline was studied in the saphenous vein and in the mesenteric artery of the dog, taking as parameters the influence of blockade of these sites on the sensitivity to and on the time for half-relaxation (t50) (both in oil and in Krebs solution) of these agonists. Preliminary experiments have shown that the t50 values are not significantly changed by the changes in the height of the contraction provided the contraction is caused by the same concentration of the agonist. The results obtained permit us to conclude that in both vessels the removal of amines depends on the concentrations used. In low (0.023 and 0.23 muM) or in moderately high (2.3 muM) concentrations, adrenaline is removed preferentially by extraneuronal sites, whereas noradrenaline "preferred" neuronal sites. The selectivity of adrenaline for extraneuronal sites was present for such low concentrations that a possible physiological role of these sites in the inactivation of circulating adrenaline must be considered. The results obtained by studying the relaxation in oil in Krebs solution and by using cortexone (60 muM) or U-0521 (dihydroxy-2-methyl propiophenone; 0.1 mM) support the view that, at least in the vein, adrenaline may accumulate in extraneuronal cells and diffuse back into the biophase during the relaxation, thereby slowing the latter. Both in the veins and in the arteries noradrenaline was inactivated more rapidly than adrenaline. The difference in the rate of inactivation of these amines, already observed in controls (when all inactivation pathways are operative) became more marked when both neuronal and extraneuronal sites were blocked. The existence of an important pathway not blocked by cocaine + cortexone + iproniazid which may preferentially inactivate noradrenaline cannot be ruled out.