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首页> 外文期刊>The journal of sexual medicine >Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study.
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Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study.

机译：内源性血管活性肽和人类阴道-分子生物学和功能研究。

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INTRODUCTION: Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. AIMS: To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. METHODS: The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 microM) on the tension induced by 0.1 microM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 microM, 0.1 microM, 1 microM) and the production of cAMP and cGMP determined by means of radioimmunoassays. MAIN OUTCOME MEASURES: Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RESULTS: RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively. CONCLUSION: Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.
机译：引言：已提出内源性肽，例如血管活性肠多肽（VIP），C型利钠肽（CNP）和缓激肽（BK），可通过使阴蒂，阴唇，阴唇，鼻中膜等松弛，从而在女性性唤醒反应中发挥作用和阴道平滑肌。虽然已经描述了内源肽对人类男性勃起组织的作用，但仅进行了很少的研究来研究女性生殖器组织（包括阴道）的肽能控制。目的：阐明在人阴道中特异性编码肽受体的mRNA的表达以及VIP，CNP和BK对孤立的人阴道壁平滑肌内皮素-1（ET-1）诱导的张力的影响。还测量了响应于组织暴露于肽而产生的环状单磷酸腺苷（cAMP）和环状单磷酸鸟苷（cGMP）的产生。方法：通过分子生物学方法（逆转录聚合酶链反应[RT-PCR]分析）研究编码VIP，CNP和BK特异受体蛋白的mRNA的表达。使用器官浴技术，研究了VIP，CNP和BK（0.1 nM至1 microM）对0.1 microM ET-1引起的人类阴道条张力的影响。还使组织暴露于三种不同浓度的VIP，CNP和BK（0.01 microM，0.1 microM，1 microM），并通过放射免疫测定法确定cAMP和cGMP的产生。主要观察指标：表征人阴道中肽受体的表达，并测定BK，CNP和VIP对分离的人阴道组织ET-1引起的收缩的松弛作用。另外，还阐明了肽对cAMP和cGMP产生的影响。结果：RT-PCR分析揭示了编码VIP受体VIP1R /血管活性肠多肽受体1型（VPAC1）和VIP2R / VPAC2，CNP受体利尿肽受体A型（NPRA），利尿肽受体B型（ NPRB）和C型利钠肽受体（NPRC），以及BK受体B2R。肽逆转了ET-1诱导的张力，其效力依次为：BK（21.7％）> VIP（20.9％）> CNP（13.3％）。 VIP和BK的放松作用与cAMP的4.8倍和5倍的增加相平行，而在CNP或BK的存在下cGMP的产生分别被刺激38倍和119倍。结论：我们的结果支持以下假设：内源性肽可能通过参与环状核苷酸依赖性途径而有助于控制人的阴道平滑肌张力。

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