Chloroethylclonidine: an irreversible agonist at prejunctional α 2 ‐adrenoceptors in rat vas deferens

1 The possibility that chloroethylclonidine (CEC) activates prejunctional α 2 ‐adrenoceptors was studied in the isolated vas deferens of the rat. Tissues were stimulated electrically and both the stimulation‐evoked overflow of tritium (after preincubation with [ 3 H]‐noradrenaline) and the purinergic contraction component (isolated by prazosin 0.3 μ m ) were measured. 2 CEC (0.1–3 μ m ) concentration‐dependently reduced the overflow of tritium evoked by trains of 6 pulses/100 Hz. The inhibition by CEC was not altered by prazosin (0.3 μ m ) but was prevented by pre‐exposure to rauwolscine (0.3 μ m ). The inhibition, once established, did not fade upon washout of CEC, even when the washout fluid contained rauwolscine (0.3 μ m ). 3 CEC (0.1–3 μ m ) concentration‐dependently reduced the purinergic component of contractions elicited by single pulses. The inhibition, again, was prevented by pre‐exposure to rauwolscine (0.3 μ m ) and once established, did not fade upon washout of CEC, even when the washout fluid contained rauwolscine (0.3 μ m ). 4 CEC (3 μ m ) reduced the overflow of tritium evoked by 20 pulses/10 Hz, did not alter the overflow evoked by 100 pulses/10 Hz and increased the overflow evoked by 500 pulses/10 Hz. 5 CEC (3 μ m ) reduced the early peak, but increased the late plateau phase, of purinergic contractions elicited by 100 pulses/10 Hz. 6 It is concluded that CEC reduces the release of noradrenaline and a purinergic co‐transmitter by irreversible activation of prejunctional α 2 ‐adrenoceptors. CEC seems to be a partial α 2 ‐agonist with an efficacy lower than that of noradrenaline. The prejunctional inhibitory effect limits the suitability of CEC for the characterization of postjunctional α 1 ‐adrenoceptors mediating responses to sympathetic nerve stimulation.