Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide is released from intrinsic nonadrenergic, noncholinergic (NANC) nerves of pig tracheal smooth muscle (TSM) in response to electrical field stimulation (EFS). In this study, we investigated the role of guanylyl cyclase in the NANC relaxation by using guanylyl cyclase inhibitors, LY83583 and methylene blue (MB). The role of large conductance calcium-activated potassium (KCa) channels in mediating NANC relaxation was studied by using inhibitors of this channel, charybdotoxin and iberiotoxin. In carbachol-contracted TSM strips, LY83583 (10-20 microM) and MB (10-100 microM) resulted in inhibition of EFS-induced relaxations at all frequencies studied. Relaxations induced by exogenous 8-Bromo-cyclic 3',5'-guanosine monophosphate (8-Br-cGMP) were unaffected by LY83583. The concentration-relaxation curves to isoproterenol, which acts by elevating adenosine-3',5'-cyclic monophosphate (cAMP), and the nitric oxide donors sodium nitroprusside (SNP) or S-nitroso-n-acetylpenicillamine (SNAP) were unaffected by LY83583. Both charybdotoxin (240 nM) and iberiotoxin (180 nM) attenuated relaxations induced by EFS and SNAP. The role of guanylyl cyclase activation in the relaxation to EFS of pig TSM is suggested by the sensitivity of the responses to MB. The selective inhibitory effects of LY83583 on relaxation to neurally released, but not to the nitric oxide donors, suggests that it acts by inhibiting nitric oxide release. The lack of any effect of LY83583 on isoproterenol- or guanosine, 3'5'-cyclic monophosphate (cGMP)-mediated relaxation suggests a mechanism that does not involve elevation of cAMP but lies proximal to the generation of cGMP. The susceptibility of the relaxations to EFS and SNAP to charybdotoxin and iberiotoxin suggests a mechanism that involves the selective activation of KCa channels in airway smooth muscle cells.
...
PMID:Modulation of nitric oxide-dependent relaxation of pig tracheal smooth muscle by inhibitors of guanylyl cyclase and calcium activated potassium channels. 754 Jul 7

1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+ concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a biphasic concentration-dependent effect on O2- generation induced by f-methionyl-leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40 microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2- generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation. 5. Addition of a high concentration of NO (40 microM) decreased authentic O2- formation by pyrogallol in a cell-free system, but a low concentration of NO (400 nM) had no effect on this. On the other hand, addition of SNP in the concentration-ranges used had no effect on authentic O2- formation by pyrogallol. 6. In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The results suggest that the enhancement observed with SNP and NO at low concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP pathway. The suppressive effect of SNP and NO at higher concentrations is mediated by the NO-induced O2--scavenging effect and activation of the guanylate cyclase-cyclic GMP pathway.
...
PMID:Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes. 758 60

In addition to mediating several physiological functions, nitric oxide (NO) has been implicated in the cytotoxicities observed following activation of macrophages or excess stimulation of neurons by glutamate. We extend our previous observations of glutamate-stimulated, NO-mediated neurotoxicity in primary cultures of rat fetal cortical, striatal, and hippocampal neurons. Neurotoxicity elicited by either NMDA or sodium nitroprusside (SNP) exhibits a similar concentration-effect relationship and time course. The concentration-effect curve of NMDA-induced neurotoxicity is shifted to the right in the presence of nitro-L-arginine and farther to the right in arginine-free media. The rank order of potency of several NO synthase (NOS) inhibitors in preventing neurotoxicity is the same as the rank order of these compounds in inhibiting NOS, and this inhibition is stereospecific. NMDA neurotoxicity is also prevented by flavoprotein inhibitors and calmodulin inhibitors, fitting with the roles of flavoproteins and calmodulin as NOS regulators. 8-Bromo-cGMP and guanylyl cyclase inhibitors do not affect neurotoxicity, while superoxide dismutase attenuates neurotoxicity. NOS neurons appear to be the source of neurotoxic NO in culture, as lesions of these neurons with 20 microM quisqualate diminish subsequent NMDA neurotoxicity. Moreover, NMDA neurotoxicity develops over time in culture coincident with the expression of NOS. Immunohistochemical localization of NOS in cultures and intact brain demonstrates widespread distribution of the cell processes suggesting that NOS neurons contact the majority of cortical neurons and so could mediate widespread neurotoxicity.
...
PMID:Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. 768 76

Involvement of endogenous nitric oxide (NO) on glutamate receptor-mediated response was investigated in neuronal cells cultured from embryonic rat hippocampus. L-NG-Nitroarginine (NOARG), a NO synthase inhibitor, augmented NMDA- and kainate-induced increase in intracellular Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorometry. However, quisqualate-induced response was not affected. The potentiating effect of NOARG was blocked by L-arginine, a substrate for NO synthase. NOARG was also effective when added after glutamate-induced response had reached a steady-state. Hemoglobin itself increased the basal level of [Ca2+]i at concentrations higher than 10 mM, and treatment of the cells with 1.0 mM hemoglobin had no effect on NMDA response. 8-Bromo-cyclic GMP was not effective on NMDA response. These results suggest that endogenous NO inhibits NMDA- and kainate-induced increase in [Ca2+]i as a negative feedback system independent of guanylate cyclase activation.
...
PMID:Endogenous nitric oxide inhibits NMDA- and kainate- responses by a negative feedback system in rat hippocampal neurons. 790 57

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:C-type natriuretic peptide stimulates catecholamine synthesis through the accumulation of cyclic GMP in cultured bovine adrenal medullary cells. 790 32

This study was designed to determine if nitric oxide (NO) has direct effects on heart rate or if it is involved in the chronotropic actions of adrenergic or cholinergic stimulation. Right atria were isolated from hearts of adult male rats, bathed in Krebs-Henseleit buffer (37 degrees C), and used to monitor spontaneous rate. For comparison, ring segments of thoracic aorta were also suspended in the Krebs-Henseleit solution and used to examine vascular actions of various agents. The dose-dependent chronotropic effects of acetylcholine (10(-7)-10(-3) M) and norepinephrine (10(-8)-3 x 10(-4) M) in right atria were not affected by pretreatment with 10(-4) M N-nitro-L-arginine or 10(-3) M N-nitro-L-arginine-methyl ester, inhibitors of L-arginine-derived NO production. SIN-1 (3-morpholino-sydnonimine), an agent which releases NO in aqueous solution, elicited a dose-dependent (0.3-100 microM) vasorelaxation in aortic preparations constricted with 60 mM KCl; the ED50 value for this effect was increased by pretreatment with methylene blue (10 microM) and LY-83,583 (6-(phenylamino)-5,8- quinolinedione; 1 and 3 microM), compounds which inhibit NO-induced stimulation of guanylate cyclase. SIN-1 produced a negative chronotropic effect in right atria; however, this action was not observed at concentrations less than 300 microM and was not antagonized by methylene blue or LY-83,583. 8-Bromo cyclic GMP produced a dose-dependent (10-3000 microM) decrease in KCl-induced tension in aortic rings. In right atria, 8-bromo cyclic GMP elicited a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Nitric oxide has no chronotropic effect in right atria isolated from rat heart. 791 42

Effects of sodium nitroprusside, 8-bromo cGMP and methylene blue on the glibenclamide-sensitive K+ current evoked by K+ channel openers in Xenopus oocytes were studied. Sodium nitroprusside (0.1-1 mM, an activator of guanylate cyclase) enhanced by 20-50% the K+ currents induced by KRN2391, nicorandil and cromakalim (K+ channel openers). 8-Bromo cGMP (1 mM) also increased the K+ current by 40-60%. Methylene blue (10 microM, an inhibitor of guanylate cyclase) irreversibly blocked the K+ current by about 20-30%. These results suggest that the activation of glibenclamide-sensitive K+ channels by K+ channel openers is modulated either positively or negatively by intracellular cGMP in oocytes.
...
PMID:Modification by cGMP of glibenclamide-sensitive K+ currents in Xenopus oocytes. 838 23

The present study was designed to investigate whether in vivo and in vitro erythropoietin (EPO) production is modulated by nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP). Serum levels of EPO in ex-hypoxic polycythemic mice were significantly increased after injections of 200 micrograms/kg sodium nitroprusside for 4 d. One injection of NG-nitro-L-arginine methyl ester (L-NAME) produced a significant dose-related decrease in serum levels of EPO in ex-hypoxic polycythemic mice in response to hypoxia. When EPO producing Hep3B cells were incubated in 1% O2 for 30 min, cGMP levels in the Hep3B cells were significantly elevated, compared with cells incubated in 20% O2. The elevation of cGMP by hypoxia was inhibited by L-NAME (100 microM). Sodium nitroprusside (10 and 100 microM) and NO (2 microM) also significantly increased cGMP levels in Hep3B cells. L-NAME, LY 83583 (6-Anilino-5,8-quinolinedione, a soluble guanylate cyclase inhibitor), and Rp-8-Bromo-cGMPS (Rp-8-Bromo-guanosine 3',5'-cyclic monophosphothioate, a cGMP-dependent protein kinase inhibitor) significantly inhibited the hypoxia-induced increase in medium levels of EPO in Hep3B cells. 8-Bromo-cGMPS produced a dose-dependent decrease in EPO messenger RNA levels in Hep3B cells in response to hypoxia. 8-Bromo-cGMP (10(-3) M) produced significant increases in medium levels of EPO in Hep3B cell cultures incubated under normoxic conditions, which was enhanced by the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (0.2 mM). These results suggest that NO and cGMP may interact in modulating hypoxic stimulation of EPO production.
...
PMID:Interaction of nitric oxide and cyclic guanosine 3',5'-monophosphate in erythropoietin production. 839 29

Effects of aminoethylisothiuronium bromide (AET), known as radioprotector, on human platelet soluble guanylate cyclase and on ADP-induced human platelets aggregation were studied. It was shown that AET - in Tris buffer and at certain pH values - is converted, via transguanidine rearrangement, to mercaptoethylguanidine. The latter contains in its molecule both the guanidine and SH groups which act as donor and acceptor of nitric oxide (NO), respectively. It was demonstrated that AET, after its rearrangement to mercaptoethylguanidine, is able to activate human platelet soluble guanylate cyclase, as well as to inhibit ADP-induced human stimulatory effect of AET is dependent on the effectiveness of its transguanidine rearrangement to mercaptoethylguanidine. The molecular mechanism of the hypotensive by - effect of AET is proposed.
...
PMID:Guanidine thiol--a new activator of soluble guanylate cyclase with antihypertensive and antiaggregatory properties. 852 55

Atrial natriuretic peptide (ANP) has been shown to inhibit the proliferation of various types of cells including glomerular mesangial cells. The activation of mitogen-activated protein kinase (MAPK) is one of the main signal transduction systems leading to cell proliferation. MAPK is tightly regulated by the activating kinase, MEK, and specific phosphatase MKP-1. Constitutive expression of MKP-1 has been shown to inhibit cell proliferation by suppressing MAPK activity. In order to understand the mechanism of the anti-proliferative effect of ANP, we examined whether ANP could inhibit MAPK by inducing MKP-1 in cultured rat glomerular mesangial cells. ANP increased the expression of MKP-1 mRNA in a dose-dependent (10 nM maximum) and time-dependent, with a peak stimulation at 30 min, manner. Receptor for ANP is a transmembrane guanylyl cyclase. Activation of guanylyl cyclase of ANP receptor by ligand plays an essential role in ANP signal transduction. 8-Bromo-cGMP, a cell permeable analogue of cyclic GMP, and sodium nitroprusside, an activator of soluble guanylyl cyclase, could mimic the effects of ANP and were able to induce the expression of MKP-1 in a similar time course as ANP. The protein expression of MKP-1 was maximally stimulated by ANP at 120 min. Treatment of the cells with ANP for 120 min resulted in an inhibition of phorbol ester-induced activation of MAPK, while the activation of MEK was not affected by ANP. These results indicate that ANP might inhibit the proliferation of mesangial cells by inactivating MAPK through the induction of MKP-1.
...
PMID:Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in glomerular mesangial cells. 855 Jun 16


<< Previous 1 2 3 4 5 6 7 8 Next >>

---