Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) and cGMP have been shown to be important mediators of penile erection. Erectile dysfunction may result from reduced or non-functional signal transduction within this cascade. There is, however, some inconsistency in the available data as mice lacking NO synthases (endothelial and neuronal nitric oxide synthase, or both) appear to be fertile whereas mice deficient in cGMP-dependent protein kinase I (PKGI) suffer from erectile dysfunction. To clarify this discrepancy we performed studies on mice lacking the NO receptor NO-sensitive guanylyl cyclase (NO-GC). In addition, we generated cell-specific NO-GC knockout (KO) lines to investigate the function of NO in individual cell types. NO-GC was specifically deleted in smooth muscle or endothelial cells (SM-guanylyl cyclase knockout (SM-GCKO) and EC-GCKO, respectively) and these KO lines were compared with total knockouts (GCKO) and wild-type animals. We investigated expression of NO-GC, NO-induced relaxation of corpus cavernosum smooth muscle and their ability to generate offspring. NO-GC-positive immunostaining was detected in smooth muscle and endothelial cells of murine corpus cavernosum but not in interstitial cells of Cajal. NO released from NO donors as well as from nitrergic neurons failed to relax precontracted corpus cavernosum from GCKO mice in organ bath experiments. Similar results were obtained in corpus cavernosum from SM-GCKO mice whereas deletion of NO-GC in endothelial cells did not affect relaxation. The lack of NO-induced relaxation in GCKO animals was not compensated for by guanosine 3,5-cyclic monophosphate (cGMP) signalling. To our surprise, GCKO males were fertile although their ability to produce offspring was decreased. Our data show that deletion of NO-GC specifically in smooth muscle cells abolishes NO-induced corpus cavernosum relaxation but does not lead to infertility.
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PMID:Preserved fertility despite erectile dysfunction in mice lacking the nitric oxide receptor. 2312 89

Cyclic guanosine monophosphate (cGMP) has been recently shown to modulate in vitro capacitation of mammalian spermatozoa, but the mechanisms through which it influences sperm functions have not been clarified. There are at least two targets of cGMP, cyclic nucleotide-gated (CNG) channels and cGMP-dependent protein kinase (PKG), involved in several physiological events in mammalian spermatozoa. It has been suggested that CNG channels allow the influx of Ca(2+) to cytoplasm during capacitation, whereas PKG could trigger a phosphorylation pathway which might also, indirectly, mediate calcium entry. Using the patch-clamp technique in whole-cell configuration, we showed how l-cis-Diltiazem (a CNG-channel inhibitor) and KT5823 (a PKG inhibitor) decreased significantly the amplitude of macroscopic ion currents in a dose-response manner, and decreased in vitro capacitation. The inhibition of CNG channels completely abolishes the Ca(2+) influx induced by cyclic nucleotides in mouse spermatozoa. This work suggests that the downstream cGMP pathway is required in mammalian sperm capacitation and the mechanisms involved include CNG channels and PKG, highlighting these molecules as important therapeutic targets for infertility treatments or to develop new male contraceptives.
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PMID:Capacitation and Ca(2+) influx in spermatozoa: role of CNG channels and protein kinase G. 2429 81

You Gui Wan (YGW) is a classic herbal formula in traditional Chinese medicine (TCM) used for the clinical treatment of infertility. This study was to explore whether YGW has an impact on mouse oocyte maturation in vitro and subsequent fertilization competence. Rat medicated serum containing YGW was prepared by orally administrating YGW. Mouse immature oocytes were cultured with YGW medicated serum and compared to those cultured with or without normal rat serum or follicle-stimulating hormone (FSH). YGW medicated serum significantly increased the percentages of matured oocytes when compared to the groups with or without normal rat serum (P < 0.01). Furthermore, YGW medicated serum increased the rate of in vitro fertilization (IVF) when compared to the groups treated with FSH and with or without normal rat serum (P < 0.001). YGW medicated serum also had significant effects on the mRNA expressions of PKA, CREB, MAPK, PKC, PKG, and MPF and the concentrations of cAMP, cGMP, and NO in matured oocytes. These results indicate that YGW can promote mouse oocyte maturation and IVF in vitro. Signaling pathways, such as the cAMP/PKA/MAPK, the PKC-MAPK, and the NO-cGMP-PKG pathway, which are similar to those induced by FSH, may be responsible for this action.
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PMID:Effect of rat medicated serum containing you gui wan on mouse oocyte in vitro maturation and subsequent fertilization competence. 2553 Jul 75