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Signaling Changes (signaling + change)
Selected AbstractsG,, that interacts with adenylyl cyclase in opioid tolerance originates from a Gs proteinDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2006Hoau-Yan Wang Abstract We previously demonstrated that chronic morphine induces a change in G protein coupling by the mu opioid receptor (MOR) from Gi/o to Gs, concurrent with the instatement of an interaction between G,, and adenylyl cyclase types II and IV. These two signaling changes confer excitatory effects on the cell in place of the typical inhibition by opioids and are associated with morphine tolerance and dependence. Both signaling changes and these behavioral manifestations of chronic morphine are attenuated by cotreatment with ultra-low-dose naloxone. In the present work, using striatum from chronic morphine-treated rats, we isotyped the G, within Gs and Go heterotrimers that coupled to MOR and compared these to the G, isotype of the G,, that interacted with adenylyl cyclase II or IV after chronic morphine treatment. Isotyping results show that chronic morphine causes a Gs heterotrimer associated with MOR to release its G,, to interact with adenylyl cyclase. These data suggest that the switch to Gs coupling by MOR in response to chronic morphine, which is attenuated by ultra-low-dose opioid antagonist cotreatment, leads to a two-pronged stimulation of adenylyl cyclase utilizing both G, and G,, subunits of the Gs protein novel to this receptor. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Calcium signaling in invertebrate glial cellsGLIA, Issue 7 2006Christian Lohr Abstract Calcium signaling studies in invertebrate glial cells have been performed mainly in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx moth Manduca sexta. The main advantages of studing glial cells in invertebrate nervous systems are the large size of invertebrate glial cells and their easy accessibility for optical and electrophysiological recordings. Glial cells in both insects and annelids express voltage-gated calcium channels and, in the case of leech glial cells, calcium-permeable neurotransmitter receptors, which allow calcium influx as one major source for cytosolic calcium transients. Calcium release from intracellular stores can be induced by metabotropic receptor activation in leech glial cells, but appears to play a minor role in calcium signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium signaling changes during postembryonic development and is essential for the migration of the glial cells, a key step in axon guidance and in stabilization of the glomerular structures that are characteristic of primary olfactory centers. © 2006 Wiley-Liss, Inc. [source] Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Muyao Li Advanced age is a major risk factor for atherosclerosis, but how aging per se influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF-1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC is not known. We previously found age-related differences in the activation of Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown to display age-related vascular pathology similar to humans, we compared IGF-1R expression in early passages of VSMC and found a constitutive activation of IGF-1R in VSMC from old compared to young rats, including IGF-1R expression and its tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from old rats to differentiate IGF-1R from other upstream signaling that could also regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD, which play important roles in the control of cell cycle arrest and stress resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment. Furthermore, IGF-1R signaling modulated these genes through activation of the Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC function in old rats and may contribute to the increased risk for atherosclerosis. J. Cell. Physiol. 217: 377,387, 2008. © 2008 Wiley-Liss, Inc. [source] Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstructionNEUROUROLOGY AND URODYNAMICS, Issue 2 2006Edward LaBelle Abstract Aims Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. Methods Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. Results The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 µM. Conclusions The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] | ||||||||||