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:2.7.11.12 (
PKG
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Effects of pharmacological modulation of protein kinase A, C and G (PKA, PKC and
PKG
) were examined on
inducible form
of nitric oxide synthase (iNOS) expressed in COS cells to elucidate regulatory mechanism of iNOS by protein kinases. Formation of nitric oxide (NO), as an index of NOS activity, was assessed by measurement of nitrite in incubation medium in long term observation and by hemoglobin assay method in kinetic study. In long term observation (18 hours), activation of PKA by 8-Br-cAMP increased NO formation that was inhibited by N-(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide (H89). Though activation of PKC by 12-O-tetradecanoyl phorbol-13-acetate (TPA) decreased NO formation, PKC inhibitor, chelerythrine, failed to inhibit the decrease. Activation of
PKG
with 8-Br-cGMP and inhibition with KT5823 resulted in no change in NO formation. Western blot analysis revealed that neither 8-Br-cAMP nor TPA affect iNOS expression. In kinetic study (short term perfusion study), no change in NO formation was observed by 8-Br-cAMP and TPA. These results indicate that, in living cells,
PKG
does not play a regulatory role in iNOS activity and that PKA and PKC do not directly modulate iNOS activity. However, PKA and PKC would possibly modify NOS activity indirectly via cofactors necessary for NO formation.
...
PMID:Protein kinase A- and C-dependent modulation of murine inducible nitric oxide synthase. 1164 42
Previous work has shown that nitric oxide (NO) mediates the antinociceptive effect of Crotalus durissus terrificus venom on carrageenin-induced hyperalgesia. In the present study the role of constitutive neuronal or of
inducible form
of nitric oxide synthase on venom effect was determined. The rat paw prostaglandin E(2) (PGE(2))-induced mechanical hyperalgesia model was used for nociceptive evaluation. The venom (200 microg/kg) administered per oz immediately before prostaglandin induced antinociception that persisted for 120 h. The characterisation of the antinociceptive effect of the venom in this model of hyperalgesia showed that kappa and delta-opioid receptors are involved in this effect. 7-nitroindazole (7-NI), a neuronal nitric oxide synthase (NOS) inhibitor, but not L-N(6)-(1-iminoethyl)lysine (L-NIL), an inhibitor of the
inducible form
of NOS, injected by intraplantar (i.pl.) route, antagonized the antinociceptive effect of the venom. The i.pl. administration of 1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a selective guanylate cyclase inhibitor, blocked antinociception, whereas Rp-cGMP triethylamine, a
cGMP-dependent protein kinase
inhibitor, partially reversed this effect. These data indicate that peripheral kappa- and delta-opioid receptors are involved in the antinociceptive effect of Crotalus durissus terrificus on prostaglandin E(2)-induced hyperalgesia. Peripheral nitric oxide, generated by neuronal NO synthase, and cGMP/PKc are responsible, at least partially, for the molecular mechanisms of venom effect.
...
PMID:Peripheral neuronal nitric oxide synthase activity mediates the antinociceptive effect of Crotalus durissus terrificus snake venom, a delta- and kappa-opioid receptor agonist. 1515 66
