Blandizzi_1993_J.Pharmacol.Exp.Ther_267_1054

The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and alpha-methylnoradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 microM, 0.88 microM, 0.93 microM and 0.83 microM, respectively. Idazoxan (1 microM), CH 38083 (1 microM), WB 4101 (1 microM), prazosin (1-10 microM) and ARC 239 (1-10 microM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated KB values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 microM), xylazine (0.1-100 microM), detomidine (0.1-100 microM) or alpha-methyl-noradrenaline (0.1-100 microM), whereas it was enhanced by idazoxan (0.1-100 microM), CH 38083 (0.1-100 microM), WB 4101 (0.1-100 microM), prazosin (0.1 microM) and ARC 239 (0.1-100 microM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine > or = detomidine > alpha-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 > or = idazoxan > CH 38083 > WB 4101 for antagonists.