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大鼠中多巴胺D2样受体激动剂诱导的阴茎勃起和打哈欠:品系的影响以及多巴胺D2受体而非D3和D4受体的作用

Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors.

作者信息

Depoortère Ronan, Bardin Laurent, Rodrigues Michael, Abrial Erika, Aliaga Monique, Newman-Tancredi Adrian

机构信息

Division of Neurobiology 2, Centre de Recherche Pierre Fabre, Castres, France.

出版信息

Behav Pharmacol. 2009 Jul;20(4):303-11. doi: 10.1097/FBP.0b013e32832ec5aa.

Abstract

Dopamine (DA) is implicated in penile erection (PE) and yawning (YA) in rats through activation of D2-like receptors. However, the exact role of each subtype (D2, D3 and D4) of this receptor family in PE/YA is still not clearly elucidated. We recorded concomitantly PE and YA after treatment with agonists with various levels of selectivity for the different subtypes of D2-like receptors. In addition, we investigated the efficacy of antagonists with selective or preferential affinity for each of the three receptor subtypes to prevent apomorphine-induced PE and YA. Wistar rats were more sensitive than Long-Evans rats to the erectogenic activity of the nonselective DA agonist apomorphine (0.01-0.08 mg/kg), whereas Sprague-Dawley rats were insensitive. However, all the three strains were equally sensitive to apomorphine-induced YA. In Wistar rats, apomorphine (0.01-0.63 mg/kg), the D2/D3 agonists quinelorane and (+)7-OH-DPAT (0.000625-10 mg/kg) or PD 128,907 (0.01-10 mg/kg), but not the D4 agonists PD-168,077, RO-10-5824 and ABT-724 (0.04-0.63 mg/kg), produced PE and YA with bell-shaped dose-response curves. Similarly, ABT-724 and CP226-269 (another D4 agonist) failed to elicit PE and YA in Sprague-Dawley rats. Furthermore, in Wistar rats, PE and YA elicited by apomorphine (0.08 mg/kg) were not modified by selective D3 (S33084 and SB-277011, 0.63-10 mg/kg) or D4 (L-745,870 and RBI-257, 0.63-2.5 mg/kg) antagonists, but were prevented by the preferential D2 blocker L-741,626 (near-full antagonism at 2.5 mg/kg). The present data do not support a major implication of either DA D3 or D4 receptors in the control of PE and YA in rats, but indicate a preponderant role of DA D2 receptors.

摘要

多巴胺(DA)通过激活D2样受体参与大鼠阴茎勃起(PE)和打哈欠(YA)过程。然而,该受体家族的每个亚型(D2、D3和D4)在PE/YA中的确切作用仍未明确阐明。我们在用对D2样受体不同亚型具有不同选择性水平的激动剂处理后,同时记录了PE和YA。此外,我们研究了对三种受体亚型中的每一种具有选择性或优先亲和力的拮抗剂预防阿扑吗啡诱导的PE和YA的效果。Wistar大鼠比Long-Evans大鼠对非选择性DA激动剂阿扑吗啡(0.01 - 0.08 mg/kg)的勃起活性更敏感,而Sprague-Dawley大鼠不敏感。然而,所有这三个品系对阿扑吗啡诱导的YA同样敏感。在Wistar大鼠中,阿扑吗啡(0.01 - 0.63 mg/kg)、D2/D3激动剂喹吡罗和(+)7 - OH - DPAT(0.000625 - 10 mg/kg)或PD 128,907(0.01 - 10 mg/kg),但不是D4激动剂PD - 168,077、RO - 10 - 5824和ABT - 724(0.04 - 0.63 mg/kg),产生了具有钟形剂量反应曲线的PE和YA。同样,ABT - 724和CP226 - 269(另一种D4激动剂)在Sprague-Dawley大鼠中未能引发PE和YA。此外,在Wistar大鼠中,阿扑吗啡(0.08 mg/kg)诱导的PE和YA不受选择性D3(S33084和SB - 277011,0.63 - 10 mg/kg)或D4(L - 745,870和RBI - 257,0.63 - 2.5 mg/kg)拮抗剂的影响,但被优先D2阻滞剂L - 741,626(2.5 mg/kg时接近完全拮抗)所阻断。目前的数据不支持DA D3或D4受体在大鼠PE和YA控制中的主要作用,但表明DA D2受体起主要作用。

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