Zhang X H, Filippi S, Vignozzi L, Morelli A, Mancina R, Luconi M, Donati S, Marini M, Vannelli G B, Forti G, Maggi M
Andrology Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
J Endocrinol. 2005 Mar;184(3):567-76. doi: 10.1677/joe.1.05885.
We recently found that the oxytocin receptor (OTR) is expressed in the human and rabbit corpus cavernosum and mediates contractility in vitro. The present study extended our investigations to the rat, and explored whether OTR regulates penile detumescence in vivo. Real-time RT-PCR quantitatively characterized the distribution of OTR mRNA in the male genital tract. Specific transcripts for OTR were expressed in all the tissues investigated. Penile expression of OTR was comparable to that observed in testis and prostate. Western blot analysis detected a single band of the expected molecular mass for OTR in all tissues examined, including rat penis. Expression of OTR protein in rat penile extracts was further confirmed by binding studies, using the OTR selective radiolabeled ligand 125I-OTA (K(d) = 17 +/- 6.5 pM, B(max)=15.7 +/- 5 fmoles/mg protein). OTR was immunolocalized to the endothelial and smooth muscle compartments of cavernous spaces and blood vessels. In rat corpus cavernosum strips, oxytocin (OT) and an OTR selective agonist ([Thr4,Gly7]OT) induced identical increases in tension, while different vasopressin agonists were less active. In vivo, OT intra-cavernous injection (ICI) dose-dependently inhibited intracavernous pressure (ICP) increase elicited by either electrical stimulation of the cavernous nerve or ICI of papaverine with similar IC(50)s (117.7 +/- 37 mU). The OTR antagonist, atosiban, counteracted the contractile effect of OT both in vitro and in vivo. Atosiban alone significantly increased ICP at lower stimulation frequencies (2 Hz = P<0.001 and 4 Hz = P<0.05 vs control), but not at the maximal frequency (16 Hz). Our data showed that OTR is present in the rat penis and mediates contractility both in vitro and in vivo, therefore suggesting a role for OT in maintaining penile detumescence.
我们最近发现,催产素受体(OTR)在人和兔的海绵体中表达,并在体外介导其收缩性。本研究将我们的调查扩展至大鼠,并探究OTR是否在体内调节阴茎消肿。实时逆转录聚合酶链反应(RT-PCR)定量分析了OTR信使核糖核酸(mRNA)在雄性生殖道中的分布。在所有研究的组织中均表达了OTR的特异性转录本。阴茎中OTR的表达与在睾丸和前列腺中观察到的相当。蛋白质免疫印迹分析在所有检测的组织中,包括大鼠阴茎,均检测到一条与OTR预期分子量相符的条带。使用OTR选择性放射性标记配体125I-OTA(解离常数K(d)=17±6.5皮摩尔,最大结合容量B(max)=15.7±5飞摩尔/毫克蛋白质)进行结合研究,进一步证实了大鼠阴茎提取物中OTR蛋白的表达。OTR免疫定位至海绵体间隙和血管的内皮及平滑肌部分。在大鼠海绵体条中,催产素(OT)和一种OTR选择性激动剂([苏氨酸4,甘氨酸7]OT)引起相同程度的张力增加,而不同的加压素激动剂活性较低。在体内,海绵体内注射OT(ICI)剂量依赖性地抑制由海绵体神经电刺激或罂粟碱ICI引起的海绵体内压(ICP)升高,其半数抑制浓度(IC(50))相似(117.7±37毫单位)。OTR拮抗剂阿托西班在体外和体内均能对抗OT的收缩作用。单独使用阿托西班在较低刺激频率下(2赫兹=与对照组相比P<0.001,4赫兹=P<0.