Dual pathways of receptor-mediated cyclic GMP generation in NG108-15 cells as differentiated by susceptibility to islet-activating protein, pertussis toxin

Kurose, Hitoshi; Ui, Michio

doi:10.1016/0003-9861(85)90183-3

Cited by 39 publications

(16 citation statements)

References 32 publications

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“…induces the production of a transferrable factor from cultured smooth muscle cells which relaxes vascular smooth muscle and stimulates the production of cyclic GMP (Schini et al, 1991). The stimulation of membrane receptors in NG 108-15 cells also increases cyclic GMP accumulation, an effect inhibited by pertussis toxin (Kurose & Ui, 1985) and a cell surface receptor activates Mg2+-dependent guanylate cyclase in the cellular slime mold Dictyostelium discoidenum (Janssens et al, 1989). …”

Section: Discussionmentioning

confidence: 99%

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Vuorinen¹,

Pörsti²,

Metsä‐Ketelä³

et al. 1992

British J Pharmacology

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1 The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on vascular tone and cyclic nucleotide accumulation of noradrenaline-precontracted endothelium-intact and endothelium-denuded rat mesenteric artery rings were compared with the effects of the known purinoceptor agonists adenosine 5'-triphosphate (ATP) and adenosine.2 GTP (10pM-1 mM) dose-dependently relaxed endothelium-intact mesenteric artery rings by producing a rapid initial response followed by sustained relaxation resembling the relaxant response to acetylcholine. GTP also slightly relaxed endothelium-denuded artery rings. The acetylcholine-and GTP-induced relaxations of endothelium-intact rings were attenuated by NG-nitro L-arginine methyl ester (L-NAME, 330pM) which attenuation was reversed with L-arginine (1 mM). 3 Guanosine (lOuM-1 mM) relaxed both endothelium-intact and -denuded artery rings in a dosedependent manner. The relaxations were more pronounced in endothelium-intact preparations and were only slightly attenuated by L-NAME (330pM). 4 ATP (1 pM-1 mM) and adenosine (1OpM-1 mM) dose-dependently relaxed endothelium-intact and -denuded artery rings. The responses were more pronounced in endothelium-intact vascular preparations.5 GTP (100pM) and guanosine (100puM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in both endothelium-intact and -denuded artery rings corresponding to the relaxations observed. The concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) were not affected. 6 ATP (100pM) increased cyclic GMP concentration of endothelium-intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100pM) and adenosine (100pM) in endothelium-intact and -denuded vascular preparations. 7 These results provide evidence that exogenous GTP and guanosine relax precontracted endotheliumintact and -denuded rat mesenteric artery rings by increasing cyclic GMP accumulation. The response to GTP of endothelium-intact rings can mainly be explained by the release of endothelium-derived relaxing factor (EDRF), but that of guanosine is only partly due to EDRF, and is a combination of endotheliumdependent and -independent effects. The endothelium-independent response of GTP and guanosine is a direct, unknown effect on smooth muscle and guanylate cyclase.

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Section: Discussionmentioning

confidence: 99%

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Vuorinen¹,

Pörsti²,

Metsä‐Ketelä³

et al. 1992

British J Pharmacology

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“…Our preliminary time-effect experiments and studies of ectonucleotidase activities in these cells are not in favour of a pure substrate effect (unpublished data). There is evidence that cGMP accumulation can increase upon the stimulation of membrane receptors in NG 108-15 cells (Kurose & Ui 1985). The existence of a cell surface receptor mediating Mg2+dependent guanylate cyclase activation in the cellular slime mold Dictyostelium discoideum has recently been proposed (Janssens el al.…”

Section: Nan02mentioning

confidence: 99%

Exogenous GTP Enhances the Effects of Sodium Nitrite on Cyclic GMP Accumulation, Vascular Smooth Muscle Relaxation and Platelet Aggregation

Laustiola

Vuorinen

Pörsti

et al. 1991

Pharmacology & Toxicology

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Exogenous guanosine triphosphate (GTP) (1-2 x 10(-4)M) resulted in increased concentrations of cyclic GMP both in endothelium denuded rat mesenteric artery (RMA) and in human ADP-stimulated platelets. Sodium nitrite (3.3 x 10(-4)M) relaxed precontracted RMA by 34%. When the arteries were preincubated with GTP (2 x 10(-4)M) sodium nitrite administration resulted in a significantly greater relaxation (58%) of the RMA with concomitant 2-fold increase in cGMP. Sodium nitrite (1 x 10(-4)M) had an inhibitory effect on ADP-induced platelet aggregation. Preincubation with GTP enhanced significantly the sodium nitrite-induced inhibition of ADP-induced platelet aggregation with a simultaneous 5-fold increase in cGMP. These results indicate that exogenous GTP enhances the sodium nitrite-induced stimulation of guanylate cyclase and thus enhances the effects of sodium nitrite on arterial smooth muscle and platelets.

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“…As far as GTN is concerned there is further support to this by the finding that the high-affinity relaxant component was attenuated by pertussis toxin (PTX) wheras the low-affinity component was not (Ahlner et al 1988). In neuroblastoma x glioma hybrid cells NG 108-15 cells it is known that the content of cGMP is increased upon stimulation of a,-adrenoceptors, muscarinic-and opiate-receptors (Kurose & Ui 1985). In this case a GTP-binding regulatory protein seems to be involved.…”

mentioning

confidence: 99%

Relaxation of Bovine Mesenteric Arteries by Glyceryl Trinitrate and Other Nitro‐Compounds: Evidence for Partly Different Mechanisms of Action

Torfgård

Ahlner

Axelsson

1990

Pharmacology & Toxicology

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The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS-5-MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 microM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS-5-MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G-protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP-lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular relaxant agents investigated.

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Dual pathways of receptor-mediated cyclic GMP generation in NG108-15 cells as differentiated by susceptibility to islet-activating protein, pertussis toxin

Cited by 39 publications

References 32 publications

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Exogenous GTP Enhances the Effects of Sodium Nitrite on Cyclic GMP Accumulation, Vascular Smooth Muscle Relaxation and Platelet Aggregation

Relaxation of Bovine Mesenteric Arteries by Glyceryl Trinitrate and Other Nitro‐Compounds: Evidence for Partly Different Mechanisms of Action

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