• Title/Summary/Keyword: Cyclic nucleotide

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Studies on the Mechanical Activities of Rabbit Myometrium V. Effects of Acetylcholine, Oxytocin and Prostagla, din F2α on Cyclic Nucleotide Levels of Rabbit Whole Uterus (가토 척출 자궁근의 운동성에 관한 연구 V. Acetylcholine, PGF2α 및 Oxytocin의 자궁 수축기전에 관한 연구)

  • Lee, Chang-Eop;Kwun, Jong-Kuk;Lee, Joong-Sup;Yang, Il-Suk;Lee, Mun-Han
    • Korean Journal of Veterinary Research
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    • v.22 no.1
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    • pp.1-8
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    • 1982
  • The effect of acetylcholine, oxytocin and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor. In the absence of MIX, acetylcholine increased guanosine 3', 5'-cyclic monophosphate (cGMP), but had no effect on adenosine 3', 5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. $PGF_{2{\alpha}}$ increased cGMP and decreased cAMP levels. MIX increased both cAMP and cGMP levels. Oxytocin and $PGF_{2{\alpha}}$ further increased cGMP levels, indicating activation of guanylate cyclase activity. The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX. Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and $PGF_{2{\alpha}}$ increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin. In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometrium plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.

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Involvement of Spontaneously Formed Cyclic Nucleotides in Cat Gastric Muscle Relaxation

  • Sim, Sang-Soo;Baek, Hye-Jung;Rhie, Duck-Joo;Yoon, Shin-Hee;Hahn, Sang-June;Jo, Yang-Hyeok;Kim, Myung-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.275-282
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    • 1999
  • Muscle strips and muscle cells from cat stomach were used to investigate whether spontaneously formed cyclic nucleotides were involved in the inhibition of gastric smooth muscle contraction. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), increased the levels of both cyclic GMP (cGMP) and cyclic AMP (cAMP) in resting state cells, while decreasing acetylcholine-induced muscle contraction. Under the influence of IBMX, SQ22536, an adenylyl cyclase inhibitor and methylene blue, a guanylyl cyclase inhibitor completely blocked increases in cAMP and cGMP respectively, without any effect on contraction. However, the combination of SQ22536 and methylene blue completely blocked increases in both cAMP and cGMP levels and stimulated contractions markedly even in the presence of IBMX. Muscle contraction inhibitors such as isoprenaline, vasoactive intestinal polypeptide and sodium nitroprusside also appeared to increase cyclic nucleotide levels which decreased contraction. Which nucleotide increased the most was dependent on the agonist used. Therefore, irrespective of the cyclic nucleotide class, the spontaneous formation of cyclic nucleotides should be considered in evaluating the mechanism of gastric smooth muscle relaxation.

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Effect of Platelet-Activating Factor on Cyclic Nucleotide Level in Rat Uterine tissue during Preimplantation Period (흰쥐의 임신초기에 있어서 자궁 조직중 Cyclic Nucleotide의 변화 및 Platelet-Activating Factor의 영향에 관한 연구)

  • Park, Kyoung-Sik;Kwun, Jong-Kuk
    • 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.

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Role of a Putative N-Glycosylation Site in Bovine Retinal Cyclic Nucleotide-Gated Channel

  • Park, Seong-Hwan;Park, Chul-Seung
    • Proceedings of the Korean Biophysical Society Conference
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    • 1997.07a
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    • pp.25-25
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    • 1997
  • Cyclic nucleotide-gated channels (CNGC's) contain a putative N-glycosylation site (Asn-X-Ser/Thr) in the linker regions connecting the fourth transmembrane domain (S4) and the ion conduction pore (P-region). This putative N-glycosylation site is highly conserved and thus found in many different CNGC in various organisms, from fruit to human.(omitted)

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Intracellular Messenger Role of Cyclic Nucleotides in Exocrine Secretion of Guinea Pig Pancreas (취외분비에 미치는 cyclic nucleotides의 역할)

  • Lee, H.W.;Kim, W.J.;Hong, S.S.
    • The Korean Journal of Pharmacology
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    • v.13 no.2
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    • pp.41-48
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    • 1977
  • In 1968, Case et al. first studied the importance of cyclic AMP as an intermediate in the action of secretin and cholecystokinin-pancreozymin and they suggested that the action of secretin, not that of cholecystokinin-pancreozymin, may be mediated through cyclic AMP. Recently Albano et al. reported that in the exocrine pancreas each of the two major physiological functions is modulated a specific cyclic nucleotide, enzyme secretion by cyclic GMP, and fluid and ionic secretion by cyclic AMP. But in pancreas still conflicting results have been reported on the role of cyclic nucleotides in enzyme and electrolyte secretion. In these study, the role of cyclic nucleotides in the exocrine pancreatic secretion was examined. The results are as follows. 1) Very strong stimulation on amylase release from guinea pig pancreatic slice was produced by 1 unit of cholecystokinin-pancreozymin but as compared to that of cholecystokinin-pancreozymin very weak response was observed by 1 unit of secretion or $1\;{\mu}g$ of VIP. 2) Both cholecystokinin-pancreozymin and acetylcholine produced a rapid and marked rise in cyclic GMP as well as cyclic AMP in isolated pancreatic tissue. However, both secretin and VIP failed to alter significantly the basal level of cyclic GMP in pancreatic fragments. 3) Atropine inhibited acetylcholine mediated amylase release, but did not affect the cholecystokinin-pancreozymin response. Furthermore, atropine pretreatment produced a marked inhibitory effect on the increase of tissue cyclic nucleotides induced by cholecystokinin-pancreozymin and acetylcholine. In summary, these results suggest that whereas the pancreatic secretion produced by secretin and VIP is modulated by the formation of cyclic AMP, the pancreatic enzyme secretion in response to cholecystokinin-pancreozymin and acetylcholine is triggered by both cyclic AMP and cyclic GMP.

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Identification and Characterization of a Putative Cyclic Nucleotide-gated Channel, CNG-1, in C. elegans

  • Cho, Suk-Woo;Cho, Jeong-Hoon;Song, Hyun-Ok;Park, Chul-Seung
    • Molecules and Cells
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    • v.19 no.1
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    • pp.149-154
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    • 2005
  • Cyclic nucleotide-gated (CNG) channels encoded by the tax-4 and tax-2 genes are required for chemosensing and thermosensing in the nematode C. elegans. We identified a gene in the C. elegans genome, which we designated cng-1, that is highly homologous to tax-4. Partial CNG-1 protein tagged with green fluorescent protein was expressed in several sensory neurons of the amphid. We created a deletion mutant of cng-1, cng-1 (jh111), to investigate its in vivo function. The mutant worms had no detectable abnormalities in terms of their basic behavior or morphology. Whereas tax-4 and tax-2 mutants failed to respond to water-soluble or volatile chemical attractants, the cng-1 null mutant exhibited normal chemotaxis to such chemicals and a tax-4;cng-1 double mutant had a similar phenotype to tax-4 single mutants. Interestingly, cng-1 and tax-4 had a synergistic effect on brood size.

Effect of Pancreatic Polypeptide Family on Cardiovascular Muscle Contractility: 1. Interactions with cyclic nucleotide activators and $K^+$ channel openers in canine cerebral arteries (Pancreatic Polypeptide Family의 심혈관계 근육 수축성에 대한 약리학적 작용: I. 개의 뇌혈관에서 cyclic nucleotide활성제와 칼륨통로개방제와의 상호작용)

  • Kim, Won-Joon;Lee, Kwang-Youn;Ha, Jeoung-Hee;Kwon, Oh-Cheol
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.147-162
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    • 1992
  • The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

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Mutant cAMP Receptor Protein Binds to DNA without DNA Bending (DNA 벤딩(휨) 없이 돌연변이 cAMP 수용체 단백질의 결합)

  • Gang, Jong-Back
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1225-1228
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    • 2006
  • Cyclic AMP receptor protein (CRP) complexed with cAMP binds to DNA and induces sharp DNA bending around ${\sim}90$ degree. Previous publication (5), however, reported that mutant CRP:cGMP complex showed high migration rate relative to mutant CRP:cAMP complex on native polyacrylamide gel. To confirm DNA structural change in the presence of CRP and cyclic nucleotide, molar cyclization factor $(j_M)$ [13] was measured with 6 constructed DNA fragments. Nonlinear regression analysis of $j_M$ data indicated that mutant CRP did not induce DNA bending in the presence of cGMP but bent DNA in the presence of cAMP without any helical twist change in DNA.