Purinergic agonists flex vas deferens muscle.
Purinergic agonists flex vas deferens muscle.
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嘌呤能激动剂使输精管肌肉弯曲。
DOI：
10.1113/jphysiol.2008.164350
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Schultz,BruceD
中科院分区：
文献类型：
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作者：
Schultz,BruceD
输精管通常被描述为一个肌肉管，其功能是作为将精子从附睾移动到尿道的管道。然而，越来越多的证据表明，这个系统要复杂得多。平滑肌张力和收缩受许多神经内分泌、内分泌和可能的光内分泌剂的影响。同样，上皮细胞的活性也会被类似的物质所改变。刺激支配雄性生殖导管的腹下神经，导致去甲肾上腺素、ATP和其他神经递质的共同释放，这些神经递质诱导或调节平滑肌收缩并可诱导上皮离子转运。事实上，有人认为生殖管中的嘌呤能受体可能是开发非甾体男性避孕药的靶点（Guret等人，2007）。因此，有很大的兴趣，在确定监管级联连接嘌呤刺激平滑肌收缩或舒张。在利用嘌呤能途径来管理男性生育能力方面的一个警告是，ATP暴露可以根据条件导致平滑肌收缩或松弛，这显然是相互矛盾的观察结果。因此，多个受体和信号级联可能参与这些反应。离子型P2 X和代谢型P2 Y受体均存在于输精管平滑肌细胞上，其具有通常与P2 X介导的Ca 2+内流相关的快速肌肉收缩。解释弛豫的级联似乎更为复杂。在最近一期的生理学杂志上，Ruan et al.（2008）提供了对可能有助于肌肉松弛的体外机制的敏锐洞察。他们的工作建立在输精管上皮有助于平滑肌对肾上腺素能刺激的反应的观察基础上（Okpalaugo et al. 2002）。这一观察结果表明，输精管平滑肌的活动可以修改的旁分泌剂从上皮细胞释放。越来越多的人认识到，神经递质和激素可以改变附睾和输精管上皮细胞的活性。事实上，神经递质，类固醇激素，肽激素和autocoids已被证明可以改变上皮细胞的离子转运。HCO 3 −分泌是特别重要的，因为它启动和支持增加精子活力。重要的是，去甲肾上腺素、ATP和腺苷已被证明可诱导阴离子分泌。阮氏论文增加了可能由生殖导管上皮介导的平滑肌张力的嘌呤能调节活动。前列腺素E2是上皮细胞对ATP依赖性反应的关键因素。这一观察结果具有深远的影响，因为前列腺素H合酶2（PGHS 2;以前称为COX 2）在输精管上皮细胞中的表达依赖于睾酮。在大鼠（McKanna et al. 1998）和人类（Kirschenbaum et al. 2000）中，输精管上皮PGHS 2表达与血清睾酮相关。PGHS 2免疫反应性存在于妊娠期和青春期后，但不存在于青春期前或去势后。最近，Pierucci-Alves & Schultz（2007）证明，睾酮暴露可增强缓激肽诱导的输精管上皮阴离子分泌（体外），这是一种由肾上腺素介导的反应。因此，睾酮诱导的上皮PGHS 2表达提供了雄激素依赖性精子发育和交付的基础。
The vas deferens is described typically as a muscular tube that functions as a conduit to move sperm from the epididymis to the urethra. A growing body of evidence, however, shows that the system is far more complex. Smooth muscle tone and contractions are affected by a number of neuocrine, endocrine and perhaps lumicrine agents. Likewise, epithelial activity is modified by a similar host of agents. Stimulation of the hypogastric nerve, which innervates the male reproductive ducts, results in the co-release of noradrenaline, ATP, and other neurotransmitters that induce or modulate smooth muscle contraction and can induce epithelial ion transport. In fact, it has been suggested that purinergic receptors in the reproductive duct might be targeted for the development of non-steroidal male contraceptives (Guret al. 2007). Thus, there is great interest in determining regulatory cascades that link purinergic stimulation to smooth muscle contraction or relaxation. One caveat in exploiting purinergic pathways to manage male fertility is the apparently conflicting observations that ATP exposure can, depending upon conditions, lead to either smooth muscle contraction or relaxation. Thus, multiple receptors and signalling cascades are probably involved in these responses. Both ionotropic P2X and metabotropic P2Y receptors are present on vas deferens smooth muscle cells with rapid muscle contraction typically associated with P2X-mediated Ca2+ entry. The cascade accounting for relaxation appears to be more complex. In a recent issue of The Journal of Physiology, Ruan et al.(2008) provide keen insight on a mechanism that probably contributes to muscle relaxation, in vitro. Their work builds on the observation that vas deferens epithelium contributes to the response of smooth muscle to adrenergic stimuli (Okpalaugo et al. 2002). This observation suggests that vas deferens smooth muscle activity can be modified by paracrine agents released from the epithelium. It is becoming more widely recognized that neurotransmitters and hormones can modify the activity of epithelial cells lining the epididymes and vas deferens. Indeed, neurotransmitters, steroid hormones, peptide hormones and autocoids have been shown to modify epithelial ion transport. HCO3− secretion is particularly important because it initiates and supports increased sperm motility. Importantly, noradrenaline, ATP and adenosine have been shown to induce anion secretion. The Ruan paper adds purinergic modulation of smooth muscle tone to the activities probably mediated by the epithelium lining the reproductive duct. Prostaglandin E2 is a key element in the epithelium-dependent response to ATP. This observation has far-reaching impact because prostaglandin H synthase 2 (PGHS2; formerly known as COX2) expression in vas deferens epithelial cells is dependent upon testosterone. In both rats (McKanna et al. 1998) and humans (Kirschenbaum et al. 2000), vas deferens epithelial PGHS2 expression correlates with serum testosterone. PGHS2 immunoreactivity is present during gestation and following puberty, but absent pre-pubertally or following castration. Recently, Pierucci-Alves & Schultz (2007) demonstrated that testosterone exposure enhances bradykinin-induced vas deferens epithelial anion secretion in vitro, a response mediated by prostaglandins. Thus, testosterone-induced epithelial PGHS2 expression provides the basis for androgen-dependent sperm development and delivery.