ALPHA-ADRENOCEPTOR-MEDIATED PREJUNCTIONAL EFFECTS OF CHLOROETHYLCLONIDINE IN THE CANINE SAPHENOUS-VEIN

The present study was undertaken to look for the effect of chloroethyl clonidine (CEC) on prejunctional alpha-2 autoreceptors of the canine s aphenous vein. The effect was tested on tritium overflow evoked by ele ctrical stimulation from tissues preloaded with 0.2 mu M H-3-norepinep hrine. Yohimbine (3-300 nM) and CEC (1-125 mu M) increased and UK-14,3 04 reduced the overflow of tritium evoked by 300 pulses (1 Hz). The ma ximal increase of tritium overflow caused by yohimbine was much higher than that caused by CEC: 3.82 and 1.74 times, respectively. CEC (5 mu M) abolished both the inhibition caused by UK-14,304 and the enhancem ent of tritium overflow caused by yohimbine. However, when CEC was add ed after yohimbine, it reduced the electrically evoked overflow of tri tium, the maximal effect being a reduction of tritium overflow by 35%. Prazosin (1-100 nM) did not change either the inhibitory effect of UK -14,304 or the facilitatory effect of CEC. These results suggest that CEC acts on two different subtypes of prejunctional alpha-2 autorecept ors; on one of them it acts as an antagonist and increases the electri cally evoked overflow of tritium (and inhibits both the effect of UK-1 4,304 and yohimbine); on the other it acts as an agonist and reduces t he electrically evoked overflow of tritium. Alternatively, one can adm it that CEC is able to inhibit alpha-2 autoreceptors, which causes an increase of the transmitter release, and to activate a nonadrenergic i nhibitory receptor thus causing a reduction of the transmitter release .