Prejunctional α2A-autoreceptors in the human gastric and ileocolic arteries

This study was undertaken to determine the subtype of prejunctional α₂-autoreceptors in human blood vessels. Segments of gastric and ileocolic arteries were incubated with ³H]noradrenaline and subsequently perifused with modified Krebs-Henseleit solution containing cocaine (12 μM). Five periods of electrical stimulation (S₁–S₅) were applied (1 Hz, 1 ms, 50 V for 1 min). Concentration-response curves for the facilitatory effect of eight α-adrenoceptor antagonists rauwolscine, 2-2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimbine, phentolamine, idazoxan, 2-(2’,6’-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101), spiroxatrine and prazosin] were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, indicating the existence of α₂-autoreceptors. The EC _30% values of the antagonists (concentrations that increased the evoked overflow of tritium by 30%) were taken as a measure of affinity to the autoreceptors. Correlations between the pEC _30% values obtained in the present study and the pK _i values of the same antagonists at cloned human α_2A-, α_2B-, α_2C-adrenoceptors expressed in Chinese hamster lung cells and at α_2D-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the α₂-autoreceptors in the human gastric and ileocolic arteries resemble most closely the α_2A-subtype. Received: 6 April 1998 / Accepted: 4 May 1998