No abstract available.
Calcium* ; Cyclic GMP* ; Muscle Cells*

No abstract available.
Cyclic GMP* ; Cytomegalovirus* ; Gene Expression* ; Humans*

Injury or inflammation affecting sensory neurons in the dorsal root ganglia (DRG) causes hyperexcitability of DRG neurons that can lead to spinal central sensitization and neuropathic pain. Recent studies have indicated that, following chronic compression of DRG (CCD) or acute dissociation of DRG (ADD) treatment, both hyperexcitability of neurons in intact DRG and behaviorally expressed hyperalgesia are maintained by activity in cGMP-PKG signaling pathway. Here, we provide evidence supporting the idea that CCD or ADD treatment activates cGMP-PKA signaling pathway in the DRG neurons. The results showed that CCD or ADD results in increase of levels of cGMP concentration and expression of PKG-I mRNA, as well as PKG-I protein in DRG. CCD or ADD treated-DRG neurons become hyperexcitable and exhibit increased responsiveness to the activators of cGMP-PKG pathway, 8-Br-cGMP and Sp-cGMP. Hyperexcitability of the injured neurons is inhibited by cGMP-PKG pathway inhibitors, ODQ and Rp-8-pCPT-cGMPS. In vivo delivery of Rp-8-pCPT-cGMPS into the compressed ganglion within the intervertebral foramen suppresses CCD-induced thermal hyperalgesia. These findings indicate that the in vivo CCD or in vitro ADD treatment can activate the cGMP-PKG signaling pathway, and that continuing activation of cGMP-PKG pathway is required to maintain DRG neuronal hyperexcitability and/or hyperalgesia after these two dissimilar forms of injury-related stress.
Animals ; Cyclic GMP ; analogs & derivatives ; metabolism ; Cyclic GMP-Dependent Protein Kinases ; metabolism ; Ganglia, Spinal ; physiopathology ; Hyperalgesia ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Thionucleotides ; metabolism

OBJECTIVETo study the effect of cGMP-dependent protein kinase (PKG) on the pathogenesis of septic shock.

METHODSConfluent endothelial cells were disintegrated and centrifugated to obtain cell lysates after being treated with LPS or PKG activator 8-Br-cGMP. PKG activity of lysates was measured with radioactive isotope label method in a reaction system of phosphorylation of specific substrate H2B by PKG, and the shape and the distribution of intracellular filamentous actin were detected by specific fluorescence staining. For the control study, the PKG specific inhibitor KT5823 was used to pretreat the endothelial cells before the administration of LPS or PKG activator 8-Br-cGMP.

RESULTSExposure to LPS for 5, 10, 30 and 60 minutes led to a rapid time-dependent increase in endothelial PKG activity (P < 0.01 compared to the blank) and the polar distribution of intracellular filamentous actin and preincubation with KT5823 abolished these effects. 8-Br-cGMP was similar to LPS.

CONCLUSIONSThe results suggested that LPS can mediate PKG activation and the stress variety of filamentous actin in the vascular endothelial cells, which probably induce the endothelial hyperpermeability after septic shock.

Capillary Permeability ; Cyclic GMP ; analogs & derivatives ; pharmacology ; Cyclic GMP-Dependent Protein Kinases ; physiology ; Cytoskeleton ; metabolism ; Endothelium, Vascular ; cytology ; metabolism ; Humans ; Lipopolysaccharides ; pharmacology ; Shock, Septic ; metabolism ; Signal Transduction

OBJECTIVESTo investigate the effects of antisense oligodeoxynucleotide(ASON) on the cyclic nucleotide monophosphates (cNMP) in smooth muscle cells of human corpus cavernosum, and provide experimental groundwork for the gene therapy of erectile dysfunction.

METHODSPDE5 gene ASON(containing exon 1) was transfected into the corpus cavernosum smooth muscle cells with the presence of liposome DOTAP. Another sense oligodeoxynucleotide(SON) and 1% of bovine serum were also transducted into the cells as controls. Two of cNMP, cAMP and cGMP, were probed and measured by ELISA at 1, 2, 4, 6, 10, 24 and 48 h after transfection.

RESULTSAfter transfection, the level of cGMP(1-6 h) in human corpus cavernosum smooth muscle cells was significantly higher than that in controls(P < 0.01).

CONCLUSIONSThe PDE5 gene ASON had been showed to manifest stimulative effect on the cGMP in smooth muscle cells of human corpus cavernosum in vitro, and it provides experimental groundwork for the gene therapy of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases ; antagonists & inhibitors ; genetics ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Humans ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; Penis ; cytology

OBJECTIVETo explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats.

METHODSTwenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry.

RESULTSThe contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01).

CONCLUSIONAging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

Aging ; physiology ; Animals ; Carbon Monoxide ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Male ; Penis ; metabolism ; Rats ; Rats, Wistar

Animals ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Male ; Myocytes, Cardiac ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Swimming

In order to investigate the correlation between traumatic servity and blood cAMP and cGMP levels in the patients with acute trauma and its clinical significance, 120 cases of trauma were randomly selected and divided into 4 groups (n = 30 in each group): mildly traumatic group (ISS < or = 9), moderately traumatic group (ISS = 10-16), severely traumatic group (ISS = 17-25) and dangerously traumatic group (> 25). The cAMP and cGMP levels were assayed in sera, leucocytes and platelets respectively in 6 h and 24 h after trauma. The results showed that cAMP and cGMP levels were elevated significantly in sera and platelets (P < 0.05 or P < 0.01), meanwhile cGMP levels in leucocytes (P < 0.05). It was concluded that cAMP and cGMP might play an important role in traumatic stress, participate in the cellular signal transducation and promote the immune function of leucocytes and the coagulation founction of platelets. Serum cAMP and cGMP levels were upregulated correspondingly as ISS increased, and positively correlated to the traumatic severity.
Blood Platelets/metabolism ; Cyclic AMP/*blood ; Cyclic GMP/*blood ; *Injury Severity Score ; Leukocytes/metabolism ; Wounds and Injuries/*blood

This study was designed to observe anoxia-induced responses and to clarify their possible mechanisms in porcine basilar and circle of Willis arteries. Anoxia produced a transient vasoconstriction, which then recovered to the basal tension of a 3-5 min. later, and the reoxygenation that follows produced the biphasic(relaxation-contraction) response in the intact endothelial rings under resting tension. The anoxia-induced contraction was potentiated by pretreatment with KC1 and PGF2alpha. Reoxygenation produced only sustained relaxation. Removal of the endothelium and pretreatment with nimodipine or indomethacine markedly attenuated the anoxia-induced contractions. Anoxia transiently and significantly increased cyclic GMP contents in the endothelium-intact preparations, but did not affect them in the endothelium-removed ones. The above results suggest that anoxia-induced contraction is endothelium-dependent and is resultant to the release of a Prostaglandin-like substance(s) .
Anoxia* ; Arteries ; Cerebral Arteries* ; Circle of Willis ; Cyclic GMP ; Dinoprost ; Endothelium ; Indomethacin ; Nimodipine ; Relaxation ; Vasoconstriction

Nitric oxide (NO) is known to mediate penile erection by activating intracellular cyclic GMP pathway. It is also suggested that cGMP pathway, on penile erection, has dominant role over the other secondary messenger pathway with cAMP, etc. Based on the hyposthesis that activation of NO-cGMP pathway could represent a more physiologic and effective approach in the treatment of erectile dysfunction, several NO donors and activator of cGMP have been used in human and animal studies of impotence. However the efficacy of those remains debatable. In the present study, we investigated the effect of NO donor [linsidomine chlorhydrate (SIN-1), S-nitroso-N-acetylpcnicillamine (SNAP), sodium nitroprusside (SNP)] alone and in combination with zaprinast (cGMP specific phosphodiesterase inhibitor) on penile erection in rats. NO donors used in this study, except SNP, did not induce penile erection sufficiently. SNP-induced penile erection is comparable to the erection induced by cavernosal nerve stimulation. However, direct applicaion of SNP in the treatment of impotence may not be acceptable as it causes a marked hypotension. Zaprinast given intracayernously either alone or in combination with NO donor may not be clinically effective. Combination with zaprinast is not shown to enhance the effect of NO donor on penile erection. Therefore, combination of NO donor with other drugs modulating different pathway may be a therapeutic approach to erectile dysfunction worthy of further investigation.
Animals ; Cyclic GMP ; Erectile Dysfunction ; Humans ; Hypotension ; Male ; Nitric Oxide* ; Nitroprusside ; Penile Erection* ; Rats* ; Tissue Donors*