Induction of c-fos and zif/268 gene expression in rat striatal neurons, following stimulation of D1-like dopamine receptors, involves protein kinase A and protein kinase C

Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons

“…Nevertheless, DR1/5-mGluR5 pathway interaction clearly depends on PKC. Although the predominant signaling pathway activated in striatal neurons by SKF38393 involves PKA (shown here in H89-mediated suppression of pERK2), DR1/5 activation of PKC has been described previously (Simpson and Morris, 1995;Gorelova and Yang, 2000) and could contribute to the observed interactions between DR1/5 and mGluR5. Overall, our data are consistent with the hypothesis that there is a shared substrate for PKA (DR1/5 activated) and PKC (mGluR5 activated) that modulates ERK2 phosphorylation.…”

Rotation and immediate-early gene expression in rats treated with the atypical D1 dopamine agonist SKF 83822

“…Although these findings must be interpreted cautiously, since it is possible that SKF 83959 may have some weak partial agonist properties (Andringa et al, 1999;Gnanalingham et al, 1995a), the simplest explanation of these data is that activation of either adenylyl cyclase or PLC may be sufficient to induce rotation and IEG expression. This notion that both signaling pathways are involved is supported by reports that D1 agonist induced Fos expression in vitro can be reduced by inhibition of either protein kinase A or protein kinase C (Simpson and Morris, 1995). One possibility is that D1 receptors linked to adenylyl cyclase and to PLC may be colocalized in individual striatal neurons and that the activity of these cells, and their production of IEGs, may be affected in a similar way by stimulation of either of these two signaling pathways.…”

“…It is possible that dopamine agonists which interact specifically with various signaling pathways may possess the useful properties of typical dopamine agonists while lacking some of their side effects. The dopamine D1 receptor agonist ABT-431, for instance, has been shown to have anti-Parkinsonian activity in humans, but also induces marked dyskinesia (Simpson and Morris, 1995). The current results suggest that selective activation of D1 receptors linked to AC is also likely to also have an anti-Parkinsonian effect; an interesting possibility is that drugs selective for AC may have less of a tendency to induce dyskinesias and other some other side effects than do agonists which also affect other signaling pathways.…”

“…In the current experiments we therefore examined whether SKF 83822 is able to reproduce two of the best established effects of standard D1 receptor agonists, namely the induction of contralateral rotation and the stimulation of expression of immediate-early genes in rats with unilateral dopamine depleting lesions. Most studies of IEG expression have examined only c-fos; under certain conditions, however, various IEGs appear to be differentially expressed (Ons et al, 2004;Pollack and Fink, 1995;Simpson and Morris, 1995). We thus examined the effects of SKF 83822 on the expression of four different IEGs, all of which have been shown to be sensitive to the effects of typical dopamine D1 agonists, in order to increase our chances of detecting unusual aspects of the response to SKF 83822.…”

Role of Adenylate and Guanylate Cyclases in β1-, β2-, and β3-Adrenoceptor-Mediated Relaxation of Internal Anal Sphincter Smooth Muscle

“…The preparations were incubated with these inhibitors for 20 to 30 min before testing the agonists. The concentrations of the antagonists were selected based on earlier studies on NF 023 (Beindl et al, 1996), NF 449 (Hohenegger et al, 1998), ODQ (Tseng et al, 2000), SQ 22536 (Pérez-Vizcaíno et al, 2002), KT 5720 (Simpson and Morris, 1995), and KT 5823 (Grider, 1993).…”