Investigation of neurotransmission in vas deferens from α 2A/D ‐adrenoceptor knockout mice

We have investigated pre‐ and post‐junctional responsiveness in vas deferens from wild‐type and α 2A/D ‐adrenoceptor knockout mice. The response to a single stimulus was not significantly different between wild‐type and knock‐out mice. The isometric contraction to 10 Hz stimulation for 4 s was significantly larger in vas deferens from knockout as compared with wild‐type. The maximum potentiation of 10 Hz stimulation‐evoked contractions by yohimbine was to 206.2±38.0% of control in wild‐type but to 135.8±13.6% of control in knockout. The α 2A/D ‐adrenoceptor selective antagonist BRL 44408 significantly increased the 10 Hz stimulation‐evoked contraction in wild‐type but not knockout, and the reverse was true for the α 2C ‐adrenoceptor selective antagonist spiroxatrine. The α 2B ‐adrenoceptor antagonist imiloxan had no effect on the evoked contraction except at high concentrations, and only in wild‐type. Following cocaine (3 μ M ) and BRL 44408 (1 μ M ), 10 Hz responses were similar in shape and maximum between wild‐type and knock‐out. The α 2 ‐adrenoceptor agonist xylazine virtually abolished the early component of the contraction to 10 Hz stimulation in the presence of nifedipine (10 μ M ) in vas deferens from knockout mice in a way consistent with a change of receptor subtype but without clear evidence for a reduced receptor number. However, the late component of the contraction to 10 Hz stimulation was significantly potentiated by xylazine in tissues from knock‐out mice. It is concluded that, although non‐α 2A/D ‐adrenoceptors replace α 2D ‐adrenoceptors in this knockout, the α 2 ‐adrenoceptor agonist and antagonist data are contradictory. The antagonist data suggest a major loss of prejunctional α 2 ‐adrenoceptors, but this is not necessarily supported by the agonist data.British Journal of Pharmacology (2002) 136 , 857–864. doi: 10.1038/sj.bjp.0704791