4-amylcinnamoylanthranilic-acid and Sneezing

Glucocorticoids (GCs) are well known for their anti-inflammatory effects, which are elicited through a transcriptional mechanism via a cytosolic glucocorticoid receptor (cGR)-mediated genomic effect. However, recent in vitro studies report that GCs can act as a membrane glucocorticoid receptor (mGR). This study aimed to examine whether mometasone furoate (MF) influences the nasal symptoms induced by histamine, substance P, ATP. Furthermore, the influences of various compounds on MF action were studied in vivo. The mice were intranasally administered with nasal symptom-inciting agents, and the occurrences of sneezing and nasal rubbing were counted. MF repressed the nasal symptoms caused when it was administered 10, 30 and 60min before the induction of nasal symptoms. The repressive effect observed 10min after the administration of MF was inhibited by RU486, a GR antagonist, but not by actinomycin D, a transcriptional inhibitor. In contrast, the repressive effect observed 60min after the administration of MF was inhibited by RU486 and actinomycin D. Therefore, the effects observed 10 and 60min after the MF administration were classified as non-genomic and genomic effects, respectively. The non-genomic effect suppressed the nasal symptoms induced by m-3M3FBS, a phospholipase C (PLC) activator, and was inhibited by U-73122, a PLC inhibitor. The genomic effect was inhibited by N-(p-amylcinnamoyl) anthranilic acid, a phospholipase A2 (PLA2) inhibitor. These results indicate that MF has a non-genomic effect through repression of the activation of PLC via the mGR, and MF has also a genomic effect that was influenced by the inhibition of PLA2 through transcriptional regulation via cGR.

Topics: Adenosine Triphosphate; Animals; Behavior, Animal; Cinnamates; Disease Models, Animal; Estrenes; Female; Genomics; Glucocorticoids; Histamine; Hormone Antagonists; Mice; Mice, Inbred ICR; Mifepristone; Mometasone Furoate; ortho-Aminobenzoates; Phospholipase A2 Inhibitors; Pregnadienediols; Pyrrolidinones; Receptors, Glucocorticoid; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sneezing; Substance P; Type C Phospholipases