PREJUNCTIONAL ALPHA(2A)-AUTORECEPTORS IN THE HUMAN GASTRIC AND ILEOCOLIC ARTERIES

This study was undertaken to determine the subtype of prejunctional al pha(2)-autoreceptors in human blood vessels. Segments of gastric and i leocolic arteries were incubated with [H-3]noradrenaline and subsequen tly perifused with modified Krebs-Henseleit solution containing cocain e (12 mu M). Five periods of electrical stimulation (S-1-S-5) were app lied (1 Hz, 1 ms; 50 V for 1 min). Concentration-response curves for t he facilitatory effect of eight cc-adrenoceptor antagonists [rauwolsci ne, 2-[2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimb ine, phentolamine, idazoxan, imethoxy-phenoxyethyl)-aminomethyl-1,4-be nzodioxan (WB4101), spiroxatrine and prazosin] were determined. All an tagonists enhanced the stimulation-evoked overflow of tritium, indicat ing the existence of alpha(2)-autoreceptors. The EC30% values of the a ntagonists (concentrations that increased the evoked overflow of triti um by 30%) were taken as a measure of affinity to the autoreceptors. C orrelations 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 lu ng cells and at alpha(2D)-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the alpha(2)-autoreceptors in t he human gastric and ileocolic arteries resemble most closely the alph a(2A)-subtype.