Prejunctional α2A-autoreceptors in the human gastric and ileocolic arteries

This study was undertaken to determine the subtype of prejunctional alpha(2)-autoreceptors in human blood vessels. Segments of gastric and ileocolic arteries were incubated with [H-3]noradrenaline and subsequently perifused with modified Krebs-Henseleit solution containing cocaine (12 mu M). Five periods of electrical stimulation (S-1-S-5) were applied (1 Hz, 1 ms; 50 V for 1 min). Concentration-response curves for the facilitatory effect of eight cc-adrenoceptor antagonists [rauwolscine, 2-[2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimbine, phentolamine, idazoxan, 2-(2',6'-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101), spiroxatrine and prazosin] were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, indicating the existence of alpha(2)-autoreceptors. The EC30% 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 alpha(2A)-, alpha(2B)-, alpha(2D)-adrenoceptors expressed in Chinese hamster lung cells and at alpha(2D)-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the alpha(2)-autoreceptors in the human gastric and ileocolic arteries resemble most closely the alpha(2A)-subtype.