NFκB has been implicated as a downstream effector of Gαq-coupled receptor signaling, but whether these and cytokine receptors activate NFκB similarly remains unclear. Stimulation of rat vascular smooth muscle cell Gαq-coupled P2Y nucleotide receptors with UTP induces luciferase transcription from a sensitive and specific NFκB dependent promoter. However, these responses are only ~ 15% of that to the reference cytokine IL-1β. IL-1β is a powerful stimulator of IκBα degradation. RelA nuclear import, and isoform specific NFκB enhancer binding in vitro, responses that are not detectable after P2Y receptor stimulation. Expression of two trans-dominant NFκB polypeptides suppresses induction of the NFκB reporter and also IL-1β stimulated monocyte chemoattractant-1 mRNA which is not induced by UTP. In contrast, UTP induces higher expression of the endogenous COX-2 and IL-6 mRNAs than does IL-1β, implying that Gαqcoupled receptor evokes additional NFκB-independent transcription factors in regulating these two genes. P2Y receptors are as effective as the reference growth factor PDGF-BB at inducing CREB, AP-1, SRE and NFAT transcription, which are largely unaffected by IL-1β treatment. NFκB is less efficiently activated then several other transcriptional effectors of Gαq coupled receptor signaling in vascular smooth muscle cells, and is instead preferentially activated by inflammatory cytokines. (C) 2000 Academic Press.
