RGD Reference Report - Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat middle cerebral arteries. - Rat Genome Database

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Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat middle cerebral arteries.

Authors: Lagaud, GJ  Lam, E  Lui, A  Van Breemen, C  Laher, I 
Citation: Lagaud GJ, etal., Biochem Biophys Res Commun. 1999 Apr 13;257(2):523-7.
RGD ID: 2293329
Pubmed: PMID:10198244   (View Abstract at PubMed)
DOI: DOI:10.1006/bbrc.1999.0350   (Journal Full-text)

Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10 microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P < 0.001). At these concentrations, PD98059 also significantly reduced the vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These results demonstrate that pressure-induced myogenic tone is inhibited by PD98059 at the concentrations that have been reported to be selective for inhibition of MEK and the MAP kinase cascade. However, our results also demonstrate that PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular smooth muscle.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of vascular associated smooth muscle contraction  IMP 2293329inhibition decreases both calcium-stimulated and unstimulated myogenic tone in middle cerebral arteries p<0.001RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
impaired smooth muscle contractility  IDA 2293329inhibition decreases both calcium-stimulated and unstimulated myogenic tone in middle cerebral arteries p<0.001RGD 
Objects Annotated

Genes (Rattus norvegicus)
Map2k1  (mitogen activated protein kinase kinase 1)


Additional Information