Endogenous Vasoactive Peptides and the Human Vagina—A Molecular Biology and Functional Study

Rahardjo, Harrina Erlianti; Brauer, A.; Mägert, Hans-Jürgen; Meyer, Markus; Kauffels, W.; Taher, Akmal; Rahardjo, Djoko; Jonas, Udo; Kuczyk, Markus A.; Ückert, Stefan

doi:10.1111/j.1743-6109.2010.01923.x

Cited by 11 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated earlier that VIP, CNP, and BK exerted only minor reversions of the tension of human vaginal smooth muscle brought about by ET‐1 . This has been explained in terms of a rapid biological degradation of these peptides by the activity of metalloendopeptidases, such as ACE/kininase II, NEP, carboxypeptidase N = CPN, and carboxypeptidase M. This study presents, for the first time, evidence that the relaxation response of the vaginal strip preparations (contracted by ET‐1) to the cumulative addition of BK, CNP, or VIP is significantly enhanced in the presence of the endopeptidase inhibitor KC 12615.…”

Section: Discussionsupporting

confidence: 55%

“…Square‐shaped strip preparations of human vaginal smooth muscle (approximately 8 mm × 4 mm × 2 mm) were mounted to the chambers (volume 10 mL) of a tissue bath system (IOA 5306, Föhr Medical Instruments GmbH, Seeheim‐Jugenheim, Germany) as has been described elsewhere . A passive tension of 10 mN (1,000 mg) was applied, followed by a resting period of 1 hour without any further mechanical manipulation.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Endopeptidase Inhibition on the Contraction–Relaxation Response of Isolated Human Vaginal Tissue

Rahardjo

Ückert

Taher

et al. 2013

The Journal of Sexual Medicine

Self Cite

View full text Add to dashboard Cite

Introduction Vasoactive peptides, such as bradykinin, C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP), and endothelin 1 (ET-1), are assumed to be involved in the control of female genital vascular and nonvascular smooth muscle. Tissue levels of said peptides are controlled by the activity of endopeptidase enzymes. Theoretically, in female genital tissues, inhibiting the degradation of bradykinin, CNP, and VIP, or the conversion of Big ET-1 into ET-1 should result in an enhancement in smooth muscle relaxation and, thus, an improvement in sexual response. Aim Elucidate the effects of the endopeptidase inhibitor KC 12615 on the contraction/relaxation response of isolated human vaginal smooth muscle to Big ET-1, bradykinin, CNP, or VIP. Methods Tissue bath experiments were carried out to ascertain the responses of human vaginal tissue challenged by ET-1 (0.1 μM) to increasing concentrations of bradykinin, CNP, and VIP (0.01 μM, 0.1 μM, and 1 μM, respectively). The effects were also evaluated following preexposure to KC 12615 (10 μM, for 20 minutes). Main Outcome Measures Measure the effects of KC 12615 on the relaxation of isolated human vaginal smooth muscle brought about by bradykinin, CNP, or VIP and the contraction mediated by Big ET-1. Results The tension induced by ET-1 was reversed by bradykinin, CNP, or VIP (−25 ± 6.6%, −13.3 ± 2.2%, and −17.6 ± 10%, respectively). Big ET-1 induced contraction of the vaginal tissue. Preexposure of the tissue to KC 12615 increased the relaxation exerted by bradykinin, CNP, or VIP (to −39.2 ± 5.8%, −40.7 ± 7.3%, and −44.6 ± 19%, respectively). The contraction induced by Big ET-1 was attenuated in the presence of KC 12615 (to approximately 25% of the initial response). Conclusion Inhibition of endopeptidase activity can antagonize the contraction of human vaginal tissue induced by Big ET-1 and increase the relaxation induced by vasoactive endogenous peptides.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

Effects of Endopeptidase Inhibition on the Contraction–Relaxation Response of Isolated Human Vaginal Tissue

Rahardjo

Ückert

Taher

et al. 2013

The Journal of Sexual Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Agonists applied to middle and upper regions of the rabbit vagina can induce strong phasic contractions, which for the rabbit vagina occurred with exposure to norepinephrine and related agonists [48] or arginine vasopressin [52] . Human vaginal smooth muscle strips from women undergoing surgery to correct prolapse were quiescent and showed sustained contractions to carbachol and endothelin-1, agonists known to increase synthesis of inositol 1, 4, 5-trisphosphate (IP 3 ) [47] , [53] . In contrast, the human vagina has been reported to exhibit phasic contractions in vivo with response frequency and amplitude increased by balloon-induced distension [30] .…”

Section: Discussionmentioning

confidence: 99%

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

et al. 2014

View full text Add to dashboard Cite

Background/AimsThe pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking.Methodology/Principal FindingsVaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina.Conclusions/SignificanceCervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

show abstract

“…Using the tissue bath technique, the peptide has been shown to produce contraction of CC tissue strips isolated from rabbit, rat and humans (Becker, Ückert, Stief, Truss, Hartmann et al., ; Matsumoto, Yoshida, Andersson, & Hedlund, ; Mumtaz et al., ). ET‐1 has also been demonstrated to act as a potent constrictor of human vaginal tissue (Rahardjo et al., , ). ET‐1 is produced by the conversion of Big ET‐1, a reaction catalysed by the endothelin‐converting enzyme (ECE), a metalloproteinase related to NEP.…”

Section: Discussionmentioning

confidence: 99%

Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue

et al. 2018

View full text Add to dashboard Cite

Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 μm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 μm), CNP and VIP (0.1 nm - 1 μm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 μm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.

show abstract

Endogenous Vasoactive Peptides and the Human Vagina—A Molecular Biology and Functional Study

Cited by 11 publications

References 32 publications

Effects of Endopeptidase Inhibition on the Contraction–Relaxation Response of Isolated Human Vaginal Tissue

Effects of Endopeptidase Inhibition on the Contraction–Relaxation Response of Isolated Human Vaginal Tissue

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue

Contact Info

Product

Resources

About