PubMed · 16240243
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G Michels, S Herzig, U C Hoppe. 2005-10-28. [Levosimendan].. https://doi.org/10.1055/s-2005-918588
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Spatial organization of signal proteins in specialized cholesterol and glycosphingolipid-enriched microdomains (lipid rafts) provide specificity in lymphocyte signalling. Src kinases associate with lipid rafts on the basis of their dual acylation in the N-terminus and initiate T cell signalling. The immunomodulatory signal enzyme protein kinase A (PKA) is a serine/threonine kinase that controls a number of processes important for immune activation by phosphorylation of substrates that alters protein-protein interactions or changes the enzymatic activity of target proteins in T cells. PKA substrates involved in immune activation include transcription factors, members of the MAP kinase pathway, phospholipases and the Src kinase Csk. The PKA type I isoenzyme localizes to lipid rafts during T cell activation and modulates directly the proximal events that take place after engagement of the T cell receptor. The most proximal and major target for PKA phosphorylation is the C-terminal Src kinase Csk which initiates a negative signal pathway that fine-tunes the T cell activation process.
Crustacean molt-inhibiting hormone (MIH), a polypeptide secreted by the X-organ/sinus gland complex of the eyestalks, regulates molting by inhibiting the synthesis of ecdysteroids by Y-organs. Previous results indicate the biosynthetic activity of Y-organs is likely controlled not only by the level of hemolymphatic MIH, but also by the responsiveness of Y-organs to MIH. The present studies were conducted to (a) identify the second messenger that mediates MIH-induced suppression of ecdysteroidogenesis, and (b) assess the possible involvement of cyclic nucleotide phosphodiesterase (PDE) in determining the responsiveness of Y-organs to MIH. Adding 8-bromo cAMP or 8-bromo cGMP to incubation medium significantly suppressed ecdysteroid production by Y-organs of the crayfish (Procambarus clarkii). Incubating Y-organs with MIH produced a significant increase in glandular cGMP, but MIH had no effect on glandular cAMP. The composite data indicate that MIH-induced suppression of ecdysteroidogenesis in Y-organs of P. clarkii is mediated by cGMP. Subsequently, Y-organs from various stages of the molt cycle were incubated with MIH, 3-isobutyl-1-methylxanthine (IBMX, an inhibitor of PDE), or both. Y-Organs from middle and late premolt stages were poorly responsive to MIH alone. Including IBMX in the incubation medium enhanced the responsiveness of the Y-organs to MIH at these stages. Moreover, glandular PDE activity in the Y-organs at these stages was significantly higher than other stages. The combined results suggest that molt cycle-associated changes in PDE activity affect the ability of MIH to stimulate cGMP accumulation and suppress ecdysteroidogenesis in Y-organs of P. clarkii.
Intracellular cyclic AMP regulation systems play an important role in the mechanisms of morphine dependence and withdrawal. In the present study, to clarify the involvement of phosphodiesterase (PDE) 4, degradation enzyme of cyclic AMP in morphine dependence and withdrawal we investigated the activities of PDE4 after naloxone-precipitation in single morphine treatment and repeated morphine treatment (morphine-dependence) rats. Naloxone (5 mg/kg, s.c.) challenge caused a significant withdrawal signs such as jumping in morphine-dependent rats following repeated treatment with morphine (4, 8, 12, and 16 mg/kg, twice a day for 4 days), but not in single morphine-treated rats (16 mg/kg, single). Naloxone challenge caused an increase in PDE4 activities in the brain of rats treated with single morphine in connection with the elevation of brain cyclic AMP. In contrast, increase in the PDE4 activities was not caused by naloxone challenge in all brain regions of morphine-dependent rats, although brain cyclic AMP was significantly increased. These results suggest that the lack of PDE4 activation leading to remarkable elevation of cyclic AMP is involved in naloxone-precipitated morphine withdrawal symptoms.