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 α-methyl-noradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 μM, 0.88 μM, 0.93 μM and 0.83 μM, respectively. Idazoxan (1 μM), CH 38083 (1 μM), WB 4101 (1 μM), prazosin (1-10 μM) and ARC 239 (1-10 μM) 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 K(B) 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 μM), xylazine (0.1-100 μM), detomidine (0.1-100 μM) or α-methyl-noradrenaline (0.1-100 μM), whereas it was enhanced by idazoxan (0.1-100 μM), CH 38083 (0.1-100 μM), WB 4101 (0.1-100 μM), prazosin (0.1 μM) and ARC 239 (0.1-100 μM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine ≥ detomidine > α-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 ≥ idazoxan > CH 38083 > WB 4101 for antagonists. The present results provide functional evidence that [3H]acetylcholine and [3H]noradrenaline release from axon terminals of guinea pig ileum myenteric plexus and noradrenergic axon terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes. On the basis of the criteria currently adopted for the classification of alpha-2 adrenoceptor subtypes, it is suggested that hetero- and auto-alpha-2 adrenoceptors investigated in the present study may resemble the alpha-2A- and alpha-2B-binding sites, respectively.
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - Dec 1 1993|
ASJC Scopus subject areas
- Molecular Medicine