Regional cyclic AMP levels in homogenates of rat brain after ketalar and trifluoperazine

Summary There was a significant fall in cAMP levels after administration of TFP or ketalar. Different amounts of cAMP were present in different regions of rat brain. Concentrations of cAMP in different regions of the rat brain were found to decrease in the following order: cerebrum > thalamus with hypothalamus > midbrain > hippocampus > cerebral cortex.Conducted under ocntract No 10.4.2 with the Polish Academy of Science.     

Regional cyclic AMP levels in homogenates of rat brain after ketalar and trifluoperazine

There was a significant fall in cAMP levels after administration of TFP or ketalar. Different amounts of cAMP were present in different regions of rat brain. Concentrations of cAMP in different regions of the rat brain were found to decrease in the following order: cerebrum > thalamus with hypothalamus > midbrain > hippocampus > cerebral cortex.     

Impaired nuclear translocation of glucocorticoid receptors: novel findings from psoriatic epidermal keratinocytes

Psoriasis is a chronic proliferative skin disease and is usually treated with topical glucocorticoids, which act through the glucocorticoid receptor (GR), a component of the physiological systems essential for immune responses, differentiation, and homeostasis. To investigate the possible role of GR in the pathogenesis of psoriasis, normal and psoriatic lesional skin were recruited. Firstly, the immunolocalization of GR in the skin and cultured epidermal keratinocytes were determined by immunofluorescence. In normal skin and cultured human epidermal keratinocytes, intracellular GR is localized in the nuclei, while in psoriatic skin and cultured keratinocytes, GR is in the cytoplasm. Next, we investigated possible factors associated with the cytoplasmic distribution. We found that VEGF and IFN-γ led to impaired nuclear translocation of GR through p53 and microtubule-inhibitor, vincristine, and inhibited nuclear uptake of GR in normal keratinocytes. In addition to dexamethasone, interleukin (IL)-13 was also able to transfer GR into nuclei of psoriatic keratinocytes. Furthermore, discontinuation of dexamethasone induced cytoplasmic retention of GR in normal keratinocytes. In contrast, energy depletion of normal epidermal keratinocytes did not change the nuclear distribution of GR. To confirm our findings in vivo, an imiquimod-induced psoriasis-like skin mouse model was included. IL-13 ameliorated (but vincristine exacerbated) the skin lesions on the mouse. Taken together, our findings define that impaired nuclear translocation of GR is associated with VEGF, IFN-γ, p53, and microtubule. Therapeutic strategies designed to accumulate GR in the nucleus, such as IL-13, may be beneficial for the therapy of psoriasis.