Prejunctional α2A-autoreceptors in the canine saphenous vein

Abstract

The aim of the study was to determine the subtype of prejunctional α₂-autoreceptors in the canine saphenous vein. Segments of the vein were incubated with ³H-noradrenaline and subsequently perifused with modified Krebs-Henseleit solution. Five periods of electrical stimulation were applied (S₁–S₅; each for 2min, 1Hz). Concentration-response curves for the inhibitory effect of the α₂-adrenoceptor agonists oxymetazoline and UK-14,304 and for the facilitatory effect of nine antagonists were determined. Correlations between the pEC_30%s for the antagonists obtained in the present study and the pK_is for the same antagonists obtained in tissues expressing only α_2A- (HT29 cells), α_2B- (neonatal rat lung), α_2C- (OK cells) or α_2D-adrenoceptors (rat submaxillary gland)showed that the α₂-autoreceptors in the canine saphenous vein resemble most closely the α_2A-subtype. Furthermore, oxymetazoline was a highly potent agonist (pIC_50%=8.10) and prazosin was a weak antagonist (pEC_30%=6.46), confirming that the α₂-adrenoceptors involved in the modulation of the response to electrical stimulation of the canine saphenous vein do not belong to either the α_2B- or α_2C-subtype. On the other hand, the EC_30% ratios phentolamine/rauwolscine and idazoxan/rauwolscine were much closer to the ratios obtained at α₂-autoreceptors of the rabbit- (α_2A) than of the guinea-pig brain cortex (α_2D). The results suggest that the sympathetic nerves of the canine saphenous vein are endowed with α_2A-adrenoceptors.