Regulation of Spontaneous Contractile Activity in the Bovine Epididymal Duct by Cyclic Guanosine 5′-Monophosphate-Dependent Pathways

Abstract

Passage of spermatozoa through the epididymis is obligatory for sperm maturation processes and is based on spontaneous phasic contractions (SC) of the epididymal duct. Here, the functional role of cyclic GMP (cGMP) signaling in modulating SC in the bovine epididymal caput and corpus region was examined by muscle tension recording and immunological and autoradiographic techniques. The cGMP-analog 8-bromo (Br)-cGMP, as well as the nitric oxide (NO) donor sodium nitroprusside and the natriuretic peptides (NPs) atrial NP and C-type NP, displayed distally increasing SC-relaxant effects. In agreement, a distally increasing epididymal expression of the cGMP-dependent protein kinase I (PKG I), endothelial NO synthase (eNOS), and the atrial NP receptor was found. Immunoreactivity for PKG, soluble guanylate cyclase, and eNOS could be localized to the epididymal muscle cells as well as to the epithelial basal cells only at the corpus level. The SC-relevant action of NO and the NPs was cGMP dependent, and the action of 8-Br-cGMP, in turn, was modified by epithelial and luminal factors. The NOS inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) caused an increase in SC frequency, indicating basal activity of NO generating enzymes. The SC-inhibitory effect of 8-Br-cGMP was clearly reduced by the PKG inhibitor Rp-8-Br-cGMPS as well as by iberiotoxin, thapsigargin, and indomethacin, pointing to PKG as main SC-relevant target of cGMP, and to large-conductance calcium-activated K(+) channels, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase and cyclooxygenase-1 as possible targets of PKG. These data support an essential role of cGMP signaling in the control of epididymal peristalsis, thereby enabling fine tuning of sperm transport and maturation.

Innervation and Immunohistochemical Characteristics of Epididymis in Alpaca Camelid (Vicugna Pacos)

“…These results agree with those reported in the cat, dog, guinea pig and human (El Badawi and Schenk, 1967;Norberg et al, 1967;Baumgarten et al, 1968;Hodson et al, 1970;Dail et al, 1993;Gürtler, 2001) including camelus dromedarius (Saleh et al, 2002). The smooth musculature of the caput and corpus epididymis displays spontanueous contraction involving cGMP in the signalling pathway (Risley, 1958;Talo, 1981;Gerendai et al, 2001;Mewe et al, 2006), while the cauda epididymis is normally quiescent until neural input is received during the ejaculatory process (Hib et al, 1982). The localization of Liguori et al cathecolaminergic fibres within the epididymis in peritubular and subepithelial regions suggests that cathecolamines play a role in neuromuscular events required for the transport of spermatozoa through the duct and for seminal emission.…”

Cyclic GMP signaling in rat urinary bladder, prostate, and epididymis: tissue-specific changes with aging and in response to Leydig cell depletion

“…The findings are consistent with and support previously reported roles for NPs in the regulation of spontaneous contractility in smooth muscle cells lining the epididymal duct (Mewe et al 2006). An apparent predominance of GC-B versus GC-A was confirmed by membrane GC assays, where CNP elicited threefold higher amounts of cGMP than ANP.…”

“…An apparent predominance of GC-B versus GC-A was confirmed by membrane GC assays, where CNP elicited threefold higher amounts of cGMP than ANP. The data probably explain at a molecular level the higher efficacy of CNP (compared with ANP) in reducing the frequency of spontaneous phasic contractions and affecting the muscle tone in bovine epididymal ducts (Mewe et al 2006). In addition to these activities operating in the control of sperm movement, recent findings elucidated a pivotal role for cGMP signaling in the epididymal epithelium, serving to regulate proton secretion into the lumen (Shum et al 2008).…”

“…Local roles for cGMP signaling comprise the regulation of muscle contractions and micturition sensations in the bladder (Persson et al 2000, Andersson & Arner 2004, Sandner et al 2009, Caremel et al 2010, the relaxation of stromal smooth muscle and control of cell proliferation in the prostate (Gradini et al 1999, Sandner et al 2009, Fibbi et al 2010, Zenzmaier et al 2010, and regulation of peristalsis and secretory epithelial cell functions in the epididymis (Mewe et al 2006, Shum et al 2008. Although certain factors implicated in cGMP pathways have been demonstrated by immunohistochemical, RT-PCR, and functional approaches, the cGMP signaling system in these organs is still poorly characterized.…”

Oral phosphodiesterase-5 inhibitors and sperm functions

“…13 Transcripts of PDE10 were found in the human testis, 14 cGMP-hydrolyzing PDE5 was localized in peritubular myoid cells of rats 15 and regulation of epididymal duct contractility by PDE3 has been suggested. 16 PDE11, the latest isoform of the PDE family that raised interest recently, 17 contains one gene, PDE11A, with four splice variants (PDE11A1-4). It was suggested that PDE11A3 is found in the testis, whereas PDE11A4 is found in the prostate.…”