• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1392-1396
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• 2005

Proteolytic digestion and CD measurement of wild-type and mutant cyclic AMP receptor proteins (CRPs) were performed either in the presence or absence of cyclic nucleotide. Results indicated that transition of a structural change to the hinge region by the binding of cAMP to the anti site was required for the binding of cAMP to the syn site near the hinge region and, although the occupancy of cAMP in the anti site increased the protein stability, CRP adopted more a stable conformation by the binding of cAMP to the syn site.

• The Korean Journal of Zoology
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• v.31 no.1
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• pp.35-48
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• 1988

This study was made to investigate the effect of testosterone and cyclic-AMP (cAMP) on rat epididymis. Peritoneai injections of testosterone and cAMP to rats were earned out The activities of acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were measured and ultrastructural changes of luminal epithelial cells were observed. As a result, the activity of ACP was significanily decreased on the third day, that of ALP on the fifth day and that of LDH on the seventh day respectively in castrated group. In addition, the activities of ACP and ALP were significanily increased when treated with testosterone for 5 days, that of LDH when treated with testosterone for 7 days. In case of cAMP and cAMP - theophylline injection, the activities of ACP and LDH were increased but the range of increase was of no significance. However a significant increase in the activity of ALP was seen on both cases. On electron microscopic examination, gradually deformed Golgi complex, destructed mitochondria and disrupted stereociha were observed in castrated group. In case of testosterone injection, disrupted Golgi complex, mitochondria and stereocilia showed recovery. When cAMP and cAMP-theophylline were injected as an alternative, various cytoplasmic organelles as well as Golgi com- plex were recovered but stereocilia remained unrecovered.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.378-384
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• 1999

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hourse. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMPon the cell cycle associated molecules (especially around G1 phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA ($10^{-7}M$) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin D1 and cdk2. The reason for the discrepancy between the H1 kinase activity and protein contents are not clear yet.

• Clinical and Experimental Reproductive Medicine
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• v.18 no.2
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• pp.133-142
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• 1991

This study was carried out to observe the change in uterine cyclic nucleotide level and the effect of PAF on cyclic nucleotides in uterine tissue in early pregnany in order to understand reciprocal relation ship between PAF and cyclic nucleotides in pregnancy in the rat. The test groups were injected intramuscularly with $1{\mu}g$ of PAF or 1.25mg of BN-52021 on day 0, 1, 2, 3, 4 and 5 of pregnancy. The level of cyclic nucleotide in removed uterine tissue was assayed by using cyclic nucleotides test kits. The results showed that the cyclic AMP content in uterine tissue of non-pregnant at pro-oestrus rat was $2.91{\pm}0.33$ pmol/mg protein which was lower than those of pregnant rat. The cyclic GMP content in uterine tissue of non-pregnant rat was $0.39{\pm}0.20$ pmol/mg pro-tein which was also lower than those of pregnant rats. The maximum level in cAMP was $5.92{\pm}1.72$ pmol/mg protein on day 3 and cGMP, $1.03{\pm}0.22$ pmol/mg protein on day 4. On each day of pregnancy, PAF induced the increased cAMP level ompared with that of intact rat. That was significant on day 0, 2 and 4 of pregnancy, p<0.05, on the other hand PAF receptor antagonist, BN-52021 ecreased cAMP level in uterine tisssue. PAF as well as BN-52021 had not an consistent effect on changes in cGMP level. These results suggest that cyclic nucleotide levels in uterine tissue ware increased during early pregnancy and PAF influences cAMP level in uterine rather than cGMP level during peri-implantation period, accordingly demonstrating a possible involvement of PAF in the regulation of implantation-related events through cAMP-mediated process.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.303-313
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• 1997

The role of the lower esophageal sphincter(LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic(NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3',5'-cyclic monophosphate(cyclic AMP) and guanosine 3',5'-cyclic mono-phosphate(cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation(EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin$(1{\mu}M)$, but not by atropine$(100{\mu}M)$, guanethidine$(100{\mu}M)$ and indomethacin$(10{\mu}M)$. The nitric oxide synthase inhibitors, $N^G-nitro-L-arginine$, $N^G-nitro-L-arginine$ methyl ester and $N^G-monomethyl-L-arginine$ inhibited EFS-induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N-ethylmaleimide(NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.11-18
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• 1994

Cyclic adenosine 3'5'-monophosphate (cyclic AMP) has been frequently accepted as an intracellular messenger for receptor-mediated action of opioids. In this experiment, it was designed to determine the interaction of dopaminergic and opioidergic system in the mouse striatum in normal and chronic haloperidol treated groups. Haloperidol 750ug/kg I.P. for 10 days was performed for dopamine denervation. The morphine, DAGO, DPDPE, and U5O,488H inhibited the increase of haloperidol-induced cyclic AMP content in chronic haloperidol treated mouse striatum. The inhibition of DAGO and DPDPE showed significant increase compared to normal mouse striatum. Naloxone showed antagonistic effect on the morphine and U5O,488H in chronic haloperidol treated group, and showed antagonistic effect on morphine, DAGO, DPDPE, and U5O, 488H in normal mouse striatum. These findings support that there is a functional interrelationship of dopaminergic and opioidergic pathway in the striatum. This result provides an evidence that following destruction of striatal dopaminergic neuron, there are some changes of cAMP content on the ${\mu},\;{\gamma},\;and\;{\kappa}$ opioid receptor, but the ${\kappa}$ opioid receptor still has its function.

• The Korean Journal of Zoology
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• v.18 no.1
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• pp.27-40
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• 1975

dbcAMP와 theophylline이 난자의 성숙을 억제하는 기작과 난자내 glycogen 함량과의 관계를 밝혀보기 위하여 실험한 결과는 다음과 같다. 1. 생쥐 여포난자의 PAS 양성물빌은 glycogen이며 핵의 성숙분열이 진행됨에 따라 glycogen의 함량은 감소한다. 2. dbcAMP나 theophylline에 의해 핵의 성숙이 억제된다 하더라도 난자내의 glycogenolysiss는 촉진된다. 이에 반해 핵분열이 일어나지 않은 난자는 배양이 진행되더라도 glycogen을 그대로 유지하고 있다. 일단 dbcAMP나 theophylline에 의해 성숙이 억제되었던 난자가 성숙과정에 들어가려면 다시 glyconeogenesis가 일어나 세포질내의 glycogen의 양이 회복하며 이때의 glycogen은 핵성숙과 더불어 소모된다. 3. Glycogen의 회복은 배양액내의 glucose 유무에 관계없이 이루어지며 따라서 이는 난자내 glucose 혹은 다른 전구물질에 의해 이루어지리라고 추측된다. 4. 결국 dbcAMP나 theophylline은 난자내 cAMP의 양을 증가시켜 glycogen의 소모를 일으키는 것으로 생각되며, glycogenolysis와 난자의 핵 성숙과정이 별개로 진행되기는 하지만 성숙의 요건은 일정량 이상의 glycogen이 함유되어 있어야 한다는 것을 알게되었다.

• Animal cells and systems
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• v.9 no.3
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• pp.173-179
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• 2005

Cyclic-AMP-dependent protein kinase (PKA) seems to function as a negative regulator of the c-Jun $NH_2-terminal$ kinase (JNK) signaling pathway. We demonstrate here that the activity of the PKA catalytic subunit (PKAc) is reduced in apoptotic PC12 pheochromocytoma cells. Apoptotic progress was inhibited by dibutyryl cyclic AMP (dbcAMP), an analog of cAMP. The rescue by dbcAMP was attributable to inhibition of the JNK but not of the p38 signaling pathway, due to the induction of PKA activity. JNK was present in immunocomplexes of PKAc, and PKAc phosphorylated JNK in vitro. Presence of p38 kinase, however, was not prominent in immunocomplexes of PKAc. Our data suggest that JNK is a target point of negative regulation by PKAc in the JNK signaling pathway.

• Mycobiology
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• v.38 no.1
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• pp.26-32
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• 2010

The cyclic AMP (cAMP) pathway plays a major role in growth, sexual differentiation, and virulence factor synthesis of pathogenic fungi. In Cryptococcus neoformans, perturbation of the cAMP pathway, such as a deletion in the gene encoding adenylyl cyclase (CAC1), causes defects in the production of virulence factors, including capsule and melanin production, as well as mating. Previously, we performed a comparative transcriptome analysis of the Ras- and cAMP- pathway mutants, which revealed 163 potential cAMP-regulated genes (38 genes at a 2-fold cutoff). The present study characterized the role of one of the cAMP pathway-dependent genes (serotype A identification number CNAG_ 06576.2). The expression patterns were confirmed by Northern blot analysis and the gene was designated cAMP-regulated gene 1 (CAR1). Interestingly, deletion of CAR1 did not affect biosynthesis of any virulence factors and the mating process, unlike the cAMP-signaling deficient cac1$\Delta$ mutant. Furthermore, the car1$\Delta$ mutant exhibited wild-type levels of the stress-response phenotype against diverse environmental cues, indicating that Car1, albeit regulated by the cAMP-pathway, is not essential to confer a cAMP-dependent phenotype in C. neoformans.

• Journal of Chest Surgery
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• v.25 no.4
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• pp.364-382
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• 1992

In order to investigate the effect of intracellular cyclic GMP on the calcium channel, whole cell patch clamp technique with internal perfusion method was used in the single ventricular myocytes of the rabbit. Cyclic GMP, cGMP analogues, cAMP, isopernaline and forskolin were perfused into cells and their effects on the calcium current were analysed by applying depolarizing step pulse of 10 mV in amplitude for 200 msec from holding potential of -40 mV. Calcium currents usually activated from -30 mV and then reached a peak at +10 mV. Amplitude of the calcium current was standardized with membrane capacitance, 50 pF. Peak amplitude at +10 mV in control was -0.15 nA/50pF. When 100 mM cAMP was applied from the pipette, peak amplitude of calcium current increased to -0.32 nA and addition of 1 mM isoprenaline further increased its amplitude. In the presence of cGMP it alone also produced an increase of the calcium current to -0.52 nA/50pF and addition of isoprenaline or forskolin increased its magnitude to -[0.55~0.95] nA/50pF. Simultaneous application of cGMP and cAMP increased the calcium current to -0.67 nA/50pF. Among the cGMP analogues, 8-Br-cGMP was the most potent stimulant for the calcium current activation. From the above results it could be concluded tlat cGMP increases the calcium current not through cAMP dependent protein kinase nor cAMP dependent phosphodiesterase pathway, but through independent phosphorylation pathway, possibly cGMP dependent protein kinase pathway.