Stress response elements (STREs, core consensus AG4 or C4T) have been demonstrated previously to occur in the upstream region of a number of genes responsive to induction by a variety of stress signals. This stress response is mediated by the homologous transcription factors Msn2p and Msn4p, which bind specifically to STREs. Double mutants (msn2 msn4) deficient in these transcription factors have been shown to be hypersensitive to severe stress conditions. To obtain a more representative overview of the set of yeast genes controlled via this regulon, a computer search of the Saccharomyces cerevisiae genome was carried out for genes, which, similar to most known STRE‐controlled genes, exhibit at least two STREs in their upstream region. In addition to the great majority of genes previously known to be controlled via STREs, 69 open reading‐frames were detected. Expression patterns of a set of these were examined by grid filter hybridization, and 14 genes were examined by Northern analysis. Comparison of the expression patterns of these genes demonstrates that they are all STRE‐controlled although their detailed expression patterns differ considerably. © 1998 John Wiley & Sons, Ltd.
1 P2Y receptors inhibiting adenylyl cyclase have been found in blood platelets, glioma cells, and endothelial cells. In platelets and glioma cells, these receptors were identi®ed as P2Y 12 . Here, we have used PC12 cells to search for adenylyl cyclase inhibiting P2Y receptors in a neuronal cellular environment. 2 ADP and ATP (0.1 ± 100 mM) left basal cyclic AMP accumulation unaltered, but reduced cyclic AMP synthesis stimulated by activation of endogenous A 2A or recombinant b 2 receptors. Forskolindependent cyclic AMP production was reduced by 41 mM and enhanced by 10 ± 100 mM ADP; this latter e ect was turned into an inhibition when A 2A receptors were blocked. 3 The nucleotide inhibition of cyclic AMP synthesis was not altered when P2X receptors were blocked, but abolished by pertussis toxin. 4 The rank order of agonist potencies for the reduction of cyclic AMP was (IC 50 values): 2-methylthio-ADP (0.12 nM)=2-methylthio-ATP (0.13 nM)4ADPbS (71 nM)4ATP (164 nM)=ADP (244 nM). The inhibition by ADP was not antagonized by suramin, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid, or adenosine-3'-phosphate-5'-phosphate, but attenuated by reactive blue 2, ATPaS, and 2-methylthio-AMP. 5 RT ± PCR demonstrated the expression of P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 , but not P2Y 1 , receptors in PC12 cells. In Northern blots, only P2Y 2 and P2Y 12 were detectable. Di erentiation with NGF did not alter these hybridization signals and left the nucleotide inhibition of adenylyl cyclase unchanged.
Bradykinin has long been known to excite sympathetic neurons via B(2) receptors, and this action is believed to be mediated by an inhibition of M-currents via phospholipase C and inositol trisphosphate-dependent increases in intracellular Ca(2+). In primary cultures of rat superior cervical ganglion neurons, bradykinin caused an accumulation of inositol trisphosphate, an inhibition of M-currents, and a stimulation of action potential-mediated transmitter release. Blockade of inositol trisphosphate-dependent signaling cascades failed to affect the bradykinin-induced release of noradrenaline, but prevented the peptide-induced inhibition of M-currents. In contrast, inhibition or downregulation of protein kinase C reduced the stimulation of transmitter release, but not the inhibition of M-currents, by bradykinin. In cultures of superior cervical ganglia, classical (alpha, betaI, betaII), novel (delta, epsilon), and atypical (zeta) protein kinase C isozymes were detected by immunoblotting. Bradykinin induced a translocation of Ca(2+)-independent protein kinase C isoforms (delta and epsilon) from the cytosol to the membrane of the neurons, but left the cellular distribution of other isoforms unchanged. This activation of Ca(2+)-independent protein kinase C enzymes was prevented by a phospholipase C inhibitor. The bradykinin-dependent stimulation of noradrenaline release was reduced by inhibitors of classical and novel protein kinase C isozymes, but not by an inhibitor selective for Ca(2+)-dependent isoforms. These results demonstrate that bradykinin B(2) receptors are linked to phospholipase C to simultaneously activate two signaling pathways: one mediates an inositol trisphosphate- and Ca(2+)-dependent inhibition of M-currents, the other one leads to an excitation of sympathetic neurons independently of changes in M-currents through an activation of Ca(2+)-insensitive protein kinase C.
Activation of P2Y receptors by released nucleotides subserves important autocrine-paracrine functions in various non
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