UMLS:C0406810 - FACTA Search

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

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The nature of neurotransmitter(s) involved in non-adrenergic non-cholinergic (NANC) relaxations induced by electrical stimulation (10 s trains, 1-8 Hz) was investigated in the precontracted longitudinal muscle-myenteric plexus preparation of the rat ileum. 2. Electrical stimulation of the tissue induced complex responses, consisting of a primary contraction, a primary relaxation, an off-relaxation and a rebound contraction, which were all tetrodotoxin(TTX)-sensitive. 3. Vasoactive intestinal polypeptide (VIP) and carbon monoxide (CO) did not induce relaxations. alpha-Chymotrypsin did not reduce the relaxations induced by electrical stimulation, while zinc protoporphyrin IX had non-specific effects. 4. Nitric oxide (NO) induced concentration-dependent relaxations. NG-nitro-L-arginine methylester (L-NAME) abolished the primary contractions and off-relaxations, while it partially reduced the primary relaxations. 5. ATP induced relaxations and ATP-desensitization of the tissues partially reduced the primary relaxations. Suramin and reactive blue 2 did not consistently influence the primary relaxations. 6. The ATP-induced relaxations were not influenced by L-NAME or TTX. The inhibitory effect of ATP-desensitization and L-NAME did not summate. 7. The cyclic AMP content of the tissue did not increase upon electrical stimulation or after addition of NO or ATP. The cyclic GMP content of the tissue increased upon electrical stimulation and addition of NO, but not after addition of ATP. 8. It is concluded that the relaxation induced by electrical stimulation consists of two types of responses. The off-relaxation is completely nitrergic, while the primary relaxation is mediated by NO, ATP and an as yet unknown transmitter which is not VIP or CO.
...
PMID:ATP and nitric oxide: inhibitory NANC neurotransmitters in the longitudinal muscle-myenteric plexus preparation of the rat ileum. 876 96

We have reported that inhibition of nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) attenuates the renin secretory response to beta adrenoceptor stimulation. We proposed that the attenuation results from disinhibition of the cyclic GMP-inhibitable isoform of phosphodiesterase (PDE III) with a resultant increase in cyclic AMP hydrolysis in the juxtaglomerular cells. In our investigation, experiments were performed in conscious rabbits to test the effects of the specific PDE III inhibitor milrinone on resting renin secretion and on the renin responses to isoproterenol and L-NAME. In the first series of experiments, infusion of milrinone increased plasma renin activity from 5.4 +/- 0.6 to 10.2 +/- 1.4 ng/ml/2 hr (P < .01). Heart rate increased markedly, but arterial pressure did not change. In the second series, infusion of isoproterenol increased plasma renin activity from 6.3 +/- 1.1 to 15.0 +/- 1.0 ng/ml/2 hr (P < .01). The renin response to isoproterenol was increased (P < .01) in the presence of milrinone (15.3 +/- 3.7 to 38.4 +/- 6.2 ng/ml/2 hr, P < .01). In the third series, L-NAME alone decreased plasma renin activity from 5.0 +/- 1.0 to 3.3 +/- 1.0 ng/ml/2 hr (P < .01). Milrinone again increased plasma renin activity and prevented the suppression of plasma renin activity by L-NAME. By contrast, milrinone did not alter the suppression of plasma renin activity produced by infusion of phenylephrine. In addition, a PDE IV inhibitor failed to prevent the suppression of PRA by L-NAME. Finally, administration of milrinone completely reversed the L-NAME-induced suppression of the renin response to isoproterenol. These results provide evidence that PDE III participates in the regulation of renin secretion, and support the proposal that the L-NAME-induced reductions in renin secretion and in the renin response to beta adrenoceptor stimulation result from disinhibition of PDE III and increased hydrolysis of cyclic AMP in the juxtaglomerular cells.
...
PMID:Role of cyclic GMP-inhibitable phosphodiesterase and nitric oxide in the beta adrenoceptor control of renin secretion. 876 33

1. When NG-nitro-L-arginine methyl ester (L-NAME, 0.1-10 nmol) or NG-monomethyl-L-arginine (L-NMMA, 10 nmol-1 mumol) was intradermally administered with bradykinin (BK, 3 nmol) into the instep of rat hind-paws, a dose-related suppression of BK-induced hyperalgesia, assessed by the paw-pressure test, was produced. 2. L-Arginine (1 mumol) but not D-arginine (1 mumol) reversed the suppressive effects of L-NAME (10 nmol) and L-NMMA (1 mumol) on BK-induced hyperalgesia. 3. Concomitant intradermal administration of BK (3 nmol) with haemoglobin (1 nmol) significantly suppressed BK-induced hyperalgesia in the paw-pressure test. The BK-induced hyperalgesia was abolished by concomitant intradermal administration of either a guanylate cyclase inhibitor, methylene blue (10 nmol), or LY83583 (1 nmol). In addition, KT5823 (1 nmol) or Rp-8-bromoguanosine-3':5'-cyclic monophosphothioate (Rp-8-Br-cGMPS; 1 nmol), an inhibitor of cyclic GMP-dependent protein kinase, also significantly suppressed BK-induced hyperalgesia. 4. The carrageenin-induced hyperalgesia was significantly attenuated by L-NAME in a dose-dependent manner. 5. L-Arginine (1 mumol), sodium nitroprusside (1 mumol), dibutyryl cyclic GMP (1 mumol) or 8-bromo cyclic GMP (1 mumol) all failed to produce any significant relieving effect on the nociceptive threshold of rodent hind-paws. Concomitant administrations of each agent with a sub-threshold dose (0.1 nmol) of BK induced significant hyperalgesia. 6. Rp-adenosine 3':5'-cyclic monophosphothioate (Rp-cAMPS; 1 nmol), an inhibitor of cyclic AMP-dependent protein kinase, significantly suppressed BK-induced mechanical hyperalgesia. Concomitant administration of forskolin (1 nmol) with 8-bromo cyclic GMP (100 nmol) induced significant hyperalgesia. 7. In the superfusion experiment of a blister base on the instep of rodent hind-paws, intradermally administered BK (3 nmol) significantly increased the outflow of both cyclic GMP and cyclic AMP from the blister base. Concomitant administrations of L-NAME (10 nmol) with BK significantly reduced the BK-induced outflow of cyclic GMP without affecting the cyclic AMP content. 8. These results suggest that the NO-cyclic GMP pathway is involved in the mechanism of BK-induced hyperalgesia, and an activation of both cyclic GMP-and cyclic AMP-second messenger system plays an important role in the production of peripherally induced mechanical hyperalgesia.
...
PMID:Involvement of endogenous nitric oxide in the mechanism of bradykinin-induced peripheral hyperalgesia. 882 27

1. In Saffan-anaesthetized rats, we have further investigated the mechanisms underlying the vasodilatation induced by adenosine in skeletal muscle by acute systemic hypoxia (breathing 8% O2 for 5 min). 2. In eleven rats the nitric oxide (NO) synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1, i.v.) reduced the increase in femoral vascular conductance (FVC) induced by hypoxia by approximately 50%. L-NAME had similar effects on the increase in FVC induced by intra-arterial (I.A.) infusion of adenosine (at 1.2 mg kg-1 min-1 for 5 min via the tail artery) and by ATP (I.A., 1 mg kg-1 min-1 for 5 min). Subsequent administration of the adenosine receptor antagonist 8-sulphophenyl theophylline (8-SPT, 20 mg kg-1, i.v.) virtually abolished the adenosine- and ATP-induced increase in FVC. 3. In a further nine rats, 8-SPT reduced the increase in FVC induced by hypoxia by approximately 50%. This remaining increase in FVC was substantially reduced by L-NAME. 4. In an additional nine rats, alpha,beta-methyleneADP (160 micrograms kg-1, i.v.) which inhibits the 5'-ectonucleotidase that degrades AMP to adenosine, reduced the peripheral vasodilatation (fall in arterial blood pressure, ABP) induced by ATP infusion, but had no effect on the increase in FVC or decrease in ABP evoked by systemic hypoxia. 5. These results provide the first evidence that the muscle vasodilatation induced by adenosine during systemic hypoxia is mainly dependent on NO synthesis. They also suggest that adenosine is released as such rather than being formed extracellularly from AMP. Given evidence that extraluminal adenosine acts in an NO-independent fashion we propose that hypoxia releases adenosine from the endothelium. Our results also indicate that hypoxia induces muscle vasodilatation that is adenosine independent but NO dependent: they allow the possibility that this is partly mediated by ATP released from the endothelium.
...
PMID:Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilatation induced in the rat by acute systemic hypoxia. 888 65

1. In rat aortic rings precontracted with phenylephrine, the beta-adrenoceptor agonist isoprenaline (10 nM to 30 microM) produces greater relaxant effects in preparations with endothelium than in endothelium-denuded preparations. The aim of this study was to determine the mechanisms involved in this effect and in particular investigate the possibility of a synergistic action between adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP). 2. Isoprenaline-induced relaxation of rat aortic rings precontracted with phenylephrine was greatly reduced by the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 300 microM) or the soluble guanylate cyclase inhibitors methylene blue (10 microM) or IH-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) but unaffected by indomethacin (10 microM), a cyclo-oxygenase inhibitor. Similarly, in intact rings, the concentration-response curve of forskolin (10 nM to 1 microM) was shifted to the right upon endothelium removal or treatment with methylene blue. 3. In endothelium-denuded rat aortic rings, isoprenaline-induced relaxation was potentiated by the guanylate cyclase activators atrial natriuretic factor (ANF, 1 to 10 nM) and sodium nitroprusside (SNP, 1 to 10 nM), and to a greater extent in the presence of the cyclic GMP-specific phosphodiesterase (PDE 5) inhibitor, 1,3dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl) pyrazolo [3,4-d] pyrimidin-4-(5H)-one (DMPPO, 30 nM). Relaxation induced by isoprenaline was also potentiated by the cyclic GMP-inhibited PDE (PDE 3) inhibitor cilostamide (100 nM). 4. Intracellular cyclic nucleotide levels were measured either in rat cultured aortic smooth muscle cells or in de-endothelialized aortic rings. In both types of preparation, isoprenaline (5 nM and 10 microM) increased cyclic AMP levels and this effect was potentiated by cilostamide (10 microM), by rolipram, a cyclic AMP-specific PDE (PDE 4) inhibitor (10 microM) and by cyclic GMP-elevating agents (50 nM ANF or 30 nM SNP plus 100 nM DMPPO). In isoprenaline-stimulated conditions, the increase in cyclic AMP induced by rolipram was further potentiated by cilostamide and by cyclic GMP-elevating agents. Cilostamide and cyclic GMP-elevating agents did not potentiate each other, suggesting a similar mechanism of action. 5. We conclude that in vascular smooth muscle (VSM) cells an increase in cyclic GMP levels may inhibit PDE 3 and, thereby, cyclic AMP catabolism. Under physiological conditions of constitutive NO release, and to a greater extent in the presence of the PDE 5 inhibitor DMPPO, cyclic GMP should act synergistically with adenylate cyclase activators to relax VSM.
...
PMID:Effects of cyclic GMP elevation on isoprenaline-induced increase in cyclic AMP and relaxation in rat aortic smooth muscle: role of phosphodiesterase 3. 889 66

1. Several previous in vivo studies demonstrated that crosslinked hemoglobin is a potent vasoconstrictor capable of significantly increasing arterial blood pressure following systemic administration. The precise mechanisms underlying the vascular effects of crosslinked hemoglobin are not clear. The present study was designed to determine the effect of crosslinked hemoglobin on the endothelial L-arginine-nitric oxide biosynthesis pathway in isolated canine arteries. 2. Isolated femoral and renal arteries were suspended in organ chambers for isometric tension recordings. Endothelium-dependent relaxations to acetylcholine and calcium ionophore A23187 were studied in the absence or in the presence of crosslinked hemoglobin or hemoglobin. A radioimmunoassay technique was used to determine levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP) and adenosine 3',5'-cyclic monophosphate (cyclic AMP). 3. A nitric oxide synthase inhibitor L-NAME (10(-4)M) selectively inhibited endothelium-dependent relaxations to acetylcholine and calcium ionophore A23187. The inhibitory effect of L-NAME was reversed by L-arginine (3 x 10(-4)M). Crosslinked hemoglobin (10(-7), 10(-6) and 10(-5)M) inhibited endothelium-dependent relaxations to acetylcholine (10(-9)-10(-5)M) or A23187 (10(-9)-10(-6)M). In the same concentration range, purified bovine hemoglobin exerted a similar inhibitory effect on relaxations mediated by activation of endothelial cells. Crosslinked hemoglobin (10(-6)M) significantly reduced basal production of cyclic GMP, but did not affect production of cyclic AMP. Acetylcholine (10(-6)M) stimulated production of cyclic GMP. This effect of acetylcholine was abolished in the presence of crosslinked hemoglobin. 4. These studies demonstrate that crosslinked hemoglobin impairs endothelium-dependent relaxations in isolated large conduit arteries. This effect appears to be mediated by the chemical antagonism of crosslinked hemoglobin against nitric oxide released from the endothelium. Inhibition of the endothelial L-arginine-nitric oxide biosynthesis pathway, with subsequent decrease of cyclic GMP in smooth muscle, may help to explain vasoconstrictor and pressor effects of crosslinked hemoglobin.
...
PMID:Crosslinked hemoglobin inhibits endothelium-dependent relaxations in isolated canine arteries. 891 36

In this study, rutaecarpine was tested for its antiplatelet activities in human platelet-rich plasma. In human platelet-rich plasma, rutaecarpine (40-200 microM) inhibited aggregation stimulated by a variety of agonists (i.e., collagen, ADP, adrenaline and arachidonic acid). The antiplatelet activity of rutaecarpine (120 microM) was not significantly attenuated by pretreatment with the nitric oxide synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA) (100 microM) or N(G)-nitro-L-arginine methyl ester (L-NAME) (200 microM) and with the guanylyl cyclase inhibitor methylene blue (100 microM). In addition, rutaecarpine (40-200 microM) did not significantly affect cyclic AMP and cyclic GMP levels in human washed platelets, whereas it significantly inhibited thromboxane B2 formation stimulated by collagen (10 microg/ml) and thrombin (0.1 U/ml). Furthermore, rutaecarpine (40-200 microM) inhibited [3H]inositol monophosphate formation stimulated by collagen and thrombin in [3H]myoinositol-loaded platelets. It is concluded that the antiplatelet effects of rutaecarpine are due to inhibition of thromboxane formation and phosphoinositide breakdown.
...
PMID:Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa. 901 40

1. The aims of this study were to compare in the rat isolated perfused lung preparation, the antagonist effects of iloprost, a stable analogue of prostacyclin, and prostaglandin E1 (PGE1) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of KATP and KCa channels and of EDRF (NO) in the effects. In addition, iloprost and PGE1 effects were compared to those of adenosine and forskolin. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5% CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) were used to block KATP, KCa channels and NO synthesis, respectively. 3. Iloprost, PGE1, adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE1 = forskolin > adenosine. EC50 values were 1.91 +/- 0.52 10(-9) M, 3.31 +/- 0.58 10(-7) M, 3.24 +/- 0.78 10(-7) M and 7.70 +/- 1.68 10(-5) M, respectively. Glibenclamide, charybdotoxin and L-NAME inhibited partially the relaxant effects of iloprost and forskolin but not those of PGE1. 4. It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE1 dilate pulmonary vessels partly through KATP channels, KCa and nitric oxide release. Furthermore our results suggest that the role of cycli AMP in these effects is not unequivocal.
...
PMID:Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat. 903 43

1. The biphasic reflex tracheal response (constriction followed by dilatation) occurred during bronchoconstriction induced by inhalation of ovalbumin antigen (OA) in sensitized guinea pigs. 2. The reflex tracheal constriction was largely reduced by atropine, and the dilatation was inhibited by propranolol and N omega-nitro-L-arginine methyl ester (L-NAME). The noradrenaline, adrenaline, cyclic AMP, and cyclic GMP contents in the tracheal segment were significantly higher during reflex tracheal dilatation. 3. These findings suggest that cholinergic nerves may mediate reflex tracheal constriction and that adrenergic and NOergic nerves may mediate the ensuing reflex tracheal dilatation.
...
PMID:Neural reflex-mediated tracheal response during bronchoconstriction induced by ovalbumin antigen in guinea pigs. 906 80

We investigated the effects of age and nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on protein kinase C (PKC), adenylyl cyclase, calcium/calmodulin-independent cyclic-AMP phosphodiesterase (cyclic-AMP PDE) and voltage-dependent L-type calcium channels in Fischer rat brain using autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]forskolin, [3H]rolipram and [3H]PN200-110 were used to label PKC, adenylyl cyclase, cyclic-AMP PDE and calcium channels, respectively. [3H]Forskolin binding significantly decreased in the striatum, hippocampal CA3 sector, dentate gyrus, hilus, thalamus, substantia nigra and cerebellum of 24-month-old (aged) rats, as compared with 6-month-old (adult) animals. [3H]Rolipram binding also showed an age-related reduction in the thalamus and cerebellum in rats. In contrast, no age-related changes were observed in [3H]PDBu and [3H]PN200-110 binding in the rat brain. Chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no significant changes in [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding in aged rat brains. However, this treatment significantly increased age-related decreases in [3H]forskolin binding in the frontal cortex; striatum and hippocampal CA1 sector in rats. The results demonstrate that [3H]forskolin binding in the rat brain is more susceptible to aging processes than [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding. Furthermore, our study shows that chronic treatment with NO inhibitor increases the age associated changes in [3H]forskolin binding in most brain areas of aged rats. These findings suggest that NO may play a key role in the regulation of adenylyl cyclase system during aging processes.
...
PMID:Effect of nitric oxide synthase inhibitor on age-related changes in second messenger systems and calcium channels in rats. 910 40

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