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

Abstract

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 μM) and BRL 44408 (1 μM), 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 μM) 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.