Investigation of neurotransmission in vas deferens from alpha(2A/D)-adrenoceptor knockout mice.
1. We have investigated pre- and post-junctional responsiveness in vas deferens from wild-type and alpha(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. 2. 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 alpha(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 alpha(2C)-adrenoceptor selective antagonist spiroxatrine. The alpha(2B)-adrenoceptor antagonist imiloxan had no effect on the evoked contraction except at high concentrations, and only in wild-type. Following cocaine (3 microM) and BRL 44408 (1 microM), 10 Hz responses were similar in shape and maximum between wild-type and knock-out. 3. The alpha(2)-adrenoceptor agonist xylazine virtually abolished the early component of the contraction to 10 Hz stimulation in the presence of nifedipine (10 microM) 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. 4. It is concluded that, although non-alpha(2A/D)-adrenoceptors replace alpha(2D)-adrenoceptors in this knockout, the alpha(2)-adrenoceptor agonist and antagonist data are contradictory. The antagonist data suggest a major loss of prejunctional alpha(2)-adrenoceptors, but this is not necessarily supported by the agonist data.
Cleary
Linda
L
Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Vandeputte
Catherine
C
Docherty
James R
JR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*; D014991:Xylazine / Q000494:pharmacology
C547769:Adra2a protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; D003042:Cocaine; D009543:Nifedipine