• Korean Journal of Veterinary Research
• /
• v.43 no.4
• /
• pp.615-624
• /
• 2003

Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.

• The Korean Journal of Pharmacology
• /
• v.30 no.3
• /
• pp.331-336
• /
• 1994

Our purpose was to know whether photo-induced adequate nitric oxide (PIANO)-mediated relaxation of rat aorta is involved in cyclic GMP increment as well as inhibition of phosphatidylinositide hydrolysis due to phenylephrine (PE). Isometric tension was measured in vitro in response to either agents that modulate NO production or release NO by photolysis of photosensitizing agents in rat aorta that had been contracted with PE submaximally. PIANO-mediated relaxation was accompanied by increment of cyclic GMP, which was dependent on the intensity and duration of light exposure and concentration of photosensitizers. Phosphatidylinositide (PI) turnover augmented by PE was significantly inhibited by PIANO. These findings indiate that cGMP increment is responsible for PIANO-mediated relaxation and which may account for the inhibition of PI turnover due to ${\alpha}-adrenergic$ receptor stimulation.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.38 no.12
• /
• pp.1724-1731
• /
• 2009

This study was aimed to investigate the effect of phyto-extract fermented mixture (MP119) on the male sexual functions. The MP119 was evaluated for anti-impotency and anti-hypertensive effects via ACE (angiotensin converting enzyme) or PDE (phosphodiesterase) inhibition assay. $IC_{50}$ values of MP119 against ACE and PDE were 241.3${\pm}$35.5 ppm and 372.2${\pm}$33.8 ppm, respectively. To investigate the effect of testosterone expression by MP119, we performed cell media test using mouse Leydig-derived TM3 cells. Production of testosterone in TM3 cell was increased by MP119. Also, NO (nitric oxide) production of HUVEC (human umbilical vein endothelial cell) was increased when MP119 was added to the cultures. Forty male ICR mice were divided into 4 groups. MP119 was orally intubated for 7 days to group 1 and 3, and same volume of vehicle to group 2 and 4 as controls. After that, group 3 and 4 were intraperitoneally injected cadmium chloride at a single dose of 2 mg/kg. On the 8th experimental day, weights of testis, epididymis and seminal vesicle, number of sperm, concentrations of serum testosterone and cGMP were determined. The number of sperm, the concentrations of testosterone and cGMP were significantly increased in two experimental groups (group 1, 3). These results suggest that MP119 enhanced the sexual function of male mice, and could protect the sexual organs from the cadmium chloride as one of the endocrine disrupters.

• Proceedings of the Ginseng society Conference
• /
• 1993.09a
• /
• pp.94-101
• /
• 1993

Lipophilic fraction(LF) from Panax ginseng C.A. Meyer inhibited the aggregation of human platelets induced by th rombin(0.1u/$m{\ell}$). LF and Molsidomine(vasodilator) induced the stimulation of cGMP - elevation and 50KD - Phosphorylation. and then the inhibition of 20KD - Phosphorylation in human platelets activated by thrombin. LF also inhibited the $Ca^{2-}-influx$ into platelets. When rat(SD : male) was fed with LF, the level of cGMP was increased in rat platelets stimulated by collagen and thrombin. On the other hand. verapamil, $Ca^{2-}-antagonist$ increased cAMP level ;n platelet stimulated by thrombin. but LF does not affected. However LF potently inhibited the thromboxane $A_2(TXA_2)$ production. The results suggest that the inhibitory effects of LF are mediated by regulation the phosphorylatior. of 50KD via cGMP-elevation and depend upon the decrease of $TXA_2$ level.

• The Journal of Korean Medicine
• /
• v.31 no.6
• /
• pp.47-57
• /
• 2010

Objective: The present study investigated the effect of ethanol extract of Cynanchum wilfordii (ECW) on vascular relaxation and vascular inflammation in rat artery isolated from rats and anti-inflammatory activity in human aortic smooth muscle cells (HASMC). Methods: Vascular tone and guanosine 3',5'-cyclic monophosphate (cGMP) production were examined in rat artery isolated from Sprague Dawley rats, in the presence of ECW. HASMC were incubated with tumor necrosis factor-alpha (TNF-${\alpha}$) or Angiotensin II for 24 h. Matrix metalloproteinase (MMP)-2 and anti-oxidant activity of ECW was investigated by pretreatment with ECW in HASMC. Results: Cumulative treatment of ECW relaxed aortic smooth muscles of rats in a dose-dependent manner. ECW-induced vasorelaxation was significantly decreased by pretreatment of L-arginine methyl ester (L-NAME) or oxadiazolo-quinoxalinone (ODQ). Furthermore, ECW treatment of thoracic aorta significantly increased cGMP production. Incubation of ECW with ODQ or L-NAME markedly decreased ECW-induced cGMP production. ECW treatment dose-dependently suppressed TNF-${\alpha}$- or Angiotensin II-induced increase in matrix metalloproteinase-2 expression in HASMC. Also, ECW exhibited 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity in vitro and reduced TNF-${\alpha}$-induced increase in reactive oxygen species production in a dose-dependent manner. Conclusions: Taken together, the results suggest that ECW exerts vascular relaxation via NO/cGMP signaling pathway and decreases MMP-2 expression via anti-oxidant activity.

• Biomolecules & Therapeutics
• /
• v.19 no.2
• /
• pp.218-223
• /
• 2011

In this study, we investigated the effect of spinach saponin-enriched fraction (SSEF) on collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation. SSEF inhibited collagen-induced platelet aggregation, and which was involved in the inhibition of thromboxane $A_2$ ($TXA_2$) production, an intracellular $Ca^{2+}$-agonist as an aggregation-inducing autacoidal molecule. In addition, SSEF significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonists as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that SSEF might inhibit $Ca^{2+}$-elevation and $TXA_2$ formation by increasing the production of $Ca^{2+}$-antagonistic molecules cAMP and cGMP. These mean that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation. On the other hand, prothrombin time (PT) and activated partial thromboplastin time (APTT) were potently prolonged by SSEF. These findings suggest that SSEF prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that SSEF may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

• Biomedical Science Letters
• /
• v.10 no.1
• /
• pp.1-8
• /
• 2004

Cordycepin separated from Cordyceps militaris is a major physiologic active component in Cordyceps militaris. The platelet aggregation is stimulated by $Ca^{2+}$, which is either mobilized from intracellular endoplasmic reticulum or transported from extracellular space. cGMP antagonizes the actions of $Ca^{2+}$. Based on these facts, we have investigated the effects of cordycepin on the mobilization of $Ca^{2+}$ and the production of cGMP on collagen ($10\mu$g/ml)-induced human platelet aggregation. Cordycepin potently stimulated the human platelet aggregation induced by collagen ($10\mu$g/ml) in a dose-dependent manner. Cordycepin (500 $\mu$M) inhibited also the collagen-induced human platelet aggregation in the presence both 1 mM and 2 mM of $CaCl_2$. These are in accord with the results that cordycepin inhibited the $Ca^{2+}$- influx on collagen-induced human platelet aggregation. These results suggest that cordycepin decrease the intracellular $Ca^{2+}$ concentration to inhibit collagen-induced human platelet aggregation. Besides, cordycepin increased the level of cGMP on collagen-induced human platelet aggregation. This result is related with the decrease of intracellular $Ca^{2+}$ concentration, because cGMP inhibits the mobilization of $Ca^{2+}$. In addition, cordycepin inhibited the human platelet aggregation induced by LY -83583, inhibitor of guanylate cyclase. This result suggested that cordycepin inhibit the platelet aggregation by stimulating the activity of guanylate cyclase. In conclusion, we demonstrated that cordycepin might have the antiplatelet function by inhibiting $Ca^{2+}$-mobilization via the stimulation of the production of cGMP.

• Journal of the Korean Society for Precision Engineering
• /
• v.25 no.12
• /
• pp.125-131
• /
• 2008

In the past, precision optical glass lenses were produced through multiple processes such as grinding and polishing, but mass production of aspheric lenses requiring high accuracy and having complex profile was rather difficult. In such a background, the high-precision optical GMP processes were developed with an eye to mass production of precision optical glass parts by molding press. Generally because the forming stage in a GMP process is operated at high temperature above $570^{\circ}C$, thermal stresses and deformations are generated in the aspheric glass lens mold that is used in GMP process. Thermal stresses and deformations have negative influences on the quality of a glass lens and mold, especially the height of the deformed glass lens will be different from the height of designed glass lens. To prevent the problems of a glass lens mold and the glass lens, it is very important that the thermal stresses and deformations of a glass lens mold at high forming temperature are considered at the glass molds design step. In this study as a fundamental study to develop the molds used in an aspheric glass lens fabrication, a heat transfer and a thermal stress analysis were carried out for the case of one cavity glass lens mold used in progressive GMP process. Finally using analysis results, it was predicted the height of thermally deformed guide ring and calculated the height of the guide ring to be modified, $64.5{\mu}m$. This result was referred to design the glass lens molds for GMP process in production field.

• Preventive Nutrition and Food Science
• /
• v.12 no.3
• /
• pp.141-147
• /
• 2007

Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is used in the treatment of various diseases such as cancer and chronic inflammation. We recently reported that cordycepin has a novel antiplatelet effect through the down regulation of $[Ca^{2+}]_{i}$ and the elevation of cGMP/cAMP production. In this study, we further investigated the effect of cordycepin on collagen-induced platelet aggregation in the presence of cGMP-dependent protein kinase (PKG)- or cAMP-dependent protein kinase (PKA)-inhibitor. PKG inhibitor Rp-8-pCPT-cGMPS potentiated the collagen-induced platelet aggregation, but PKA inhibitor Rp-8-Br-cAMPS did not. However, both Rp-8-pCPT-cGMPS and Rp-8-Br-cAMPS reduced inhibition by cordycepin of collagen-induced platelet aggregation. Moreover, cordycepin inhibited $Ca^{2+}-dependent$ phosphorylation of both 47 kDa- and 20 kDa-protein in the presence of both PKG inhibitor and PKA inhibitor. Taken altogether, these results suggest that the inhibitory effect of cordycepin on collagen-induced platelet aggregation is associated with cGMP/PKG- and cAMP/PKA-pathways, and thus cordycepin may be an efficacious intervention against platelet aggregation-mediated thrombotic disease.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.6
• /
• pp.811-821
• /
• 2020

Mycobacterium tuberculosis produces mycolic acids which are relevant for persistence, recalcitrance to antibiotics and defiance to host immunity. c-di-GMP is a second messenger involved in transition from planktonic cells to biofilms, whose levels are controlled by diguanylate cyclases (DGC) and phosphodiesterases (PDE). The transcriptional regulator dosR, is involved in response to low oxygen, a condition likely happening to a subset of cells within biofilms. Here, we found that in M. bovis BCG, expression of both BCG1416c and BCG1419c genes, which code for a DGC and a PDE, respectively, decreased in both stationary phase and during biofilm production. The kasA, kasB, and fas genes, which are involved in mycolic acid biosynthesis, were induced in biofilm cultures, as was dosR, therefore suggesting an inverse correlation in their expression compared with that of genes involved in c-di-GMP metabolism. The relative abundance within trehalose dimycolate (TDM) of α-mycolates decreased during biofilm maturation, with methoxy mycolates increasing over time, and keto species remaining practically stable. Moreover, addition of synthetic c-di-GMP to mid-log phase BCG cultures reduced methoxy mycolates, increased keto species and practically did not affect α-mycolates, showing a differential effect of c-di-GMP on keto- and methoxy-mycolic acid metabolism.