• Title/Summary/Keyword: Adenylate cyclase

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Mechanism of Pituitary Adenylate Cyclase-Activating Polypeptide-Induced Inhibition on Catecholamine Secretion Evoked by Cholinergic Stimulation and Membrane Depolarization in the Rat Adrenal Gland

  • Lim, Dong-Yoon;Kang, Jeong-Won;Kim, Young-Jo
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.339-350
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    • 1999
  • The present study was attempted to examine the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. The perfusion of PACAP (10 nM) into an adrenal vein for 60 min produced a great inhibition in CA secretion evoked by ACh $(5.32{\times}10^{-3}\;M),$ high $K^+\;(5.6{\times}10^{-2}\;M),$ DMPP $(10^{-4}\;M\;for\;2\;min),$ McN-A-343 $(10^{-4}\;M\;for\;2\;min),$ cyclopiazonic acid $(10^{-5}\;M\;for\;4\;min)$ and Bay-K-8644 $(10^{-5}\;M\;for\;4\;min).$ Also, in the presence of neuropeptide (NPY), which is known to be co-localized with norepinephrine in peripheral sympathetic nerves, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with PACAP (10 nM) under the presence of VIP antagonist $[(Lys^1,\;Pro^{2.5},\;Arg^{3.4},\;Tyr^6)-VIP\;(3\;{\mu}M)]$ for 20 min, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not altered greatly in comparison to the case of PACAP-treatment only. Taken together, these results suggest that PACAP causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells.

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The use of pituitary adenylate cyclase-activating polypeptide in the pre-maturation system improves in vitro developmental competence from small follicles of porcine oocytes

  • Park, Kyu-Mi;Kim, Kyu-Jun;Jin, Minghui;Han, Yongquan;So, Kyoung-Ha;Hyun, Sang-Hwan
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.12
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    • pp.1844-1853
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    • 2019
  • Objective: We investigated how pituitary adenylate cyclase-activating polypeptide (PACAP) affects embryonic development during pre-in vitro maturation (pre-IVM) using porcine oocytes isolated from small follicles. Methods: We divided the follicles into the experimental groups by size (SF, small follicles; MF, medium follicles) and treated with and without PACAP and cultured for 18 hours (PreSF[-]PACAP; without PACAP, Pre-SF[+]PACAP; with PACAP) before undergoing IVM. The gene expression related to extracellular matrix formation (amphiregulin, epiregulin, and hyaluronan synthase 2 [HAS2]) and apoptosis (Bcl-2-associated X [BAX], B-cell lymphoma 2, and cysteine-aspartic acid protease 3) was investigated after maturation. The impact on developmental competence was assessed by the cleavage and blastocyst rate and total cell number of blastocysts in embryos generated from parthenogenesis (PA) and in vitro fertilization (IVF). Results: Cleavage rates in the Pre-SF(+)PACAP after PA were significantly higher than SF and Pre-SF(-)PACAP (p<0.05). The cleavage rates between MF and Pre- SF(+)PACAP groups yielded no notable differences after IVF. Pre-SF(+)PACAP displayed the higher rate of blastocyst formation and greater total cell number than SF and Pre-SF(-)PACAP (p<0.05). Cumulus cells showed significant upregulation of HAS2 mRNA in the Pre-SF(+)PACAP compared to the SF (p<0.05). In comparison to other groups, the Pre-SF(+)PACAP group displayed a downregulation in mRNA expression of BAX in matured oocytes (p<0.05). Conclusion: The PACAP treatment during pre-IVM improved the developmental potential of porcine oocytes derived from SF by regulating cumulus expansion and apoptosis of oocytes.

Carbon Metabolism and Its Global Regulation in Corynebacterium glutamicum (Corynebacterium glutamicum의 탄소대사 및 총체적 탄소대사 조절)

  • Lee, Jung-Kee
    • Microbiology and Biotechnology Letters
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    • v.38 no.4
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    • pp.349-361
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    • 2010
  • In this review, the current knowledge of the carbon metabolism and global carbon regulation in Corynebacterium glutamicum are summarized. C. gluamicum has phosphotransferase system (PTS) for the utilization of sucrose, glucose, and fructose. C. glutamicum does not show any preference for glucose when various sugars or organic acids are present with glucose, and thus cometabolizes glucose with other sugars or organic acids. The molecular mechanism of global carbon regulation such as carbon catabolite repression (CCR) in C. glutamicum is quite different to that in Gram-negative or low-GC Gram-positive bacteria. GlxR (glyoxylate bypass regulator) in C. glutamicum is the cyclic AMP receptor protein (CRP) homologue of E. coli. GlxR has been reported to regulate genes involved in not only glyoxylate bypass, but also central carbon metabolism and CCR including glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle. Therefore, GlxR has been suggested as a global transcriptional regulator for the regulation of diverse physiological processes as well as carbon metabolism. Adenylate cyclase of C. glutamicum is a membrane protein belonging to class III adenylate cyclases, thus it could possibly be a sensor for some external signal, thereby modulating cAMP level in response to environmental stimuli. In addition to GlxR, three additional transcriptional regulators like RamB, RamA, and SugR are also involved in regulating the expression of many genes of carbon metabolism. Finally, recent approaches for constructing new pathways for the utilization of new carbon sources, and strategies for enhancing amino acid production through genetic modification of carbon metabolism or regulatory network are described.

THE RECIPROCAL EFFECTS OF SEVERAL GINSENOSIDES ON THE ADENYLATE CYCLASE AND GUANYLATE CYCLASE (몇가지 진세노사이드들이 Adenyl 산 고리화효소 및 Guanyl산 고리화 효소에 미치는 상반적인 효과)

  • Park Inown;Lee Youn Young;Lee Kwang Seung;Seo Kih Lim;Cha Mi Kyung
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.107-111
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    • 1984
  • 쥐의 뇌에서 추출한 입자상 아데닐산 고리화효소와 입자상 구아닐산효소의 활동성에 미치는 몇 가지 긴세노시드들의 효과를 조사하였다. $Rb_{2},\;Rb_{1}$, Rc 및 Re들과 같은 약간의 진세노사이드들이 두 효소들의 활동성을 상반적으로 변화시키는 것을 관찰하였다. 아데닐산 고리화효소와 구아닐산 고리화효소의 활동성에 미치는 GMP 및 AMP의 조절작용을 조사하였다. 긴세노시드 Rd로 방해된 아데닐산고리화효소는 GMP를 첨가함에 따라서 활성화되었다. 마찬가지로. 긴세노시드 $Rb_{2}$로 방해된 아데닐산 고리화효소도 GMP에 의해서 활성화되었다. 다른 한편, 긴세노시드 Rc로 활성화된 구아닐산 고리화효소는 AMP 또는 GMP를 첨가함에 따라서 방해되었다. 진세노사이드 $Rb_{2}$ 도파민 사이에는 아데닐산 고리화효소 계상의 수용체들에의 결함에 있어서 경쟁적이라는 것을 알았다. 이 결과는 긴세노시드 $Rb_{2}$가 세포의 D-1 도파민 수용체에 특이하게 결합한다는 것을 말해 준다.

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Carbon monoxide activates large-conductance calcium-activated potassium channels of human cardiac fibroblasts through various mechanisms

  • Bae, Hyemi;Kim, Taeho;Lim, Inja
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.3
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    • pp.227-237
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    • 2021
  • Carbon monoxide (CO) is a cardioprotectant and potential cardiovascular therapeutic agent. Human cardiac fibroblasts (HCFs) are important determinants of myocardial structure and function. Large-conductance Ca2+-activated K+ (BK) channel is a potential therapeutic target for cardiovascular disease. We investigated whether CO modulates BK channels and the signaling pathways in HCFs using whole-cell mode patch-clamp recordings. CO-releasing molecules (CORMs; CORM-2 and CORM-3) significantly increased the amplitudes of BK currents (IBK). The CO-induced stimulating effects on IBK were blocked by pre-treatment with specific nitric oxide synthase (NOS) blockers (L-NG-monomethyl arginine citrate and L-NG-nitroarginine methyl ester). 8-bromo-cyclic GMP increased IBK. KT5823 (inhibits PKG) or ODQ (inhibits soluble guanylate cyclase) blocked the CO-stimulating effect on IBK. Moreover, 8-bromo-cyclic AMP also increased IBK, and pre-treatment with KT5720 (inhibits PKA) or SQ22536 (inhibits adenylate cyclase) blocked the CO effect. Pre-treatment with N-ethylmaleimide (a thiol-alkylating reagent) also blocked the CO effect on IBK, and DL-dithiothreitol (a reducing agent) reversed the CO effect. These data suggest that CO activates IBK through NO via the NOS and through the PKG, PKA, and S-nitrosylation pathways.

Calcitonin Gene-related Peptide Suppresses Pacemaker Currents by Nitric Oxide/cGMP-dependent Activation of ATP-sensitive K+ Channels in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • Choi, Seok;Parajuli, Shankar Prasad;Yeum, Cheol Ho;Park, Chan Guk;Kim, Man Yoo;Kim, Young Dae;Cha, Kyoung Hun;Park, Young Bong;Park, Jong Seong;Jeong, Han Seong;Jun, Jae Yeoul
    • Molecules and Cells
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    • v.26 no.2
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    • pp.181-185
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    • 2008
  • The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at $30^{\circ}C$. Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive $K^+$ channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive $K^+$ channels. Nitric oxide- and guanylate cyclase-dependent pathways are involved in these effects.

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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Effect of cAMP on the Differentiation of F9 Teratocarcinoma Stem Cells Induced by Ginsenosides (Ginsenosides에 의한 F9 기형암종세포의 분화유도 과정에서 cAMP의 작용)

  • 이열남;이호영
    • Journal of Ginseng Research
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    • v.21 no.3
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    • pp.141-146
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    • 1997
  • The role of cAMP in the differentiation process of F9 cells induced by ginsenosides was examined by performing transient transfixion assay with CRE-luciferase reporter plasmid, GR thansactivation assay with GRE-luciferase activity with or without treatment of CAMP and forskolin, an activator of adenylate cyclase, and protein klnase A assay in the presence of ginsenosides. Ginsenosides had no effect on CRE-transactivation activity, whereas retinoic acid induced the activity. When cAMP or forskolin was treated with ginsenosides, GRE-luciferase activity was further augumented by them. In addition, ginsenosides induced protein kinase A activity in the presence of cAMP. These results suggest that ginsenosides activate cAMP-dependent protein kinase A which, in turn, increase GR activity in F9 cells.

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Purification and Characterization of the $\beta$-Adrenergic Receptor from Rat Cerebral Cortex

  • 신찬영;김희진;노민수;함경수;강현삼;고광호
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.292-292
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    • 1994
  • Catecholamines acting through ${\beta}$-adrenergic receptors regulate a wide range of metabolic activities in mammalian tissue. Of the various receptors coupled to adenylate cyclase, the ${\beta}$-adrenergic receptors are the most extensively characterized and have been purified from both nonmammal ian and mammal inn sources. However, most studies of the molecular properties of ${\beta}$-adrenergic receptors have been confined to peripheral tissues. Less progress has been achieved in characterizing the brain ${\beta}$-adrenergic receptor The goal of the present study was, therefore, to purify and characterize the neurotransmitter receptor proteins. To achieve this goal, the following stepwise experiments were performed. At first, the membrane-bound ${\beta}$-adrenergic receptors were. solubi1ized from brain tissue. Secondly, conditions for affinity chromatography were determined to purify the solubilized receptors effectively. Finally, the large-scale purification was performed and the characteristics of the purified ${\beta}$-adrenergic receptor were examined.

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