Alter neurotransmitter release via phosphorlyation of

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Alter neurotransmitter release via phosphorlyation of synapsin Regulate protein synthesis by phosphorylation of ribosomes Active the transcription factor CREB and affect gene expression DAG activates protein kinase C (PKC) PKC has many forms Some are DAG dependent only and some are dependent on DAG & Ca++ PKC is involved in cell growth & differentiation
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Gq Intracellular Cascade Gq receptor activation by ligand binding activates PLC PLC causes PIP2 to breakdown into IP3 & DAG IP3 can release intracellular stores of Ca++ DAG can activate PKC
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Gq
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Enzymatic Receptor Activation Best characterized for the neurotrophins Enzymatic receptor is membrane bound and is activated by ligand binding The activation triggers the dimerization of two receptors which then autophosphorylate and activate intracellular signaling molecules Via linker proteins (not sure how) the phosphorylated receptor complex activates small molecular weight G-proteins The activation of the small molecular weight G-proteins (via phosphorylation) triggers a molecular switch Controls cellular events such as Growth factors in the cell Cellular stress responses Vesicle trafficking & exocytosis Regulation of protein synthesis at ribosomes Nuclear trafficking of RNA & protein
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Enzymatic Receptor Cascade
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Trk Receptors
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Hormone Receptors Traditional hormone receptors are in the cytosol Steroid hormones are lipophillic and can travel through the membrane into the cytosol of the cell Upon ligand binding they are activated Once activated they travel to the nucleus and act as transcription factors by binding to the DNA
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Lipid soluble messengers have special binding proteins for transport in blood have special binding proteins for communication of message to cell E.G. Steroid Hormone Binding Protein (SHBP; SBP)
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Steroid receptors always act as transcription factors i.e. change protein levels… long-term effects SBP = steroid binding protein (transport in blood) R = cytoplasmic receptor for steroid 90 = heat shock protein 90; critical for translocation HRE = hormone response element Steroid Receptors
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Steroid Hormones All steroids are derived from cholesterol and are lipid soluble
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Regulation of Steroid Levels Steroid hormones are never stored. Steroids are released as they are synthesized. Levels of steroid are regulated by control (e.g. phosphorylation) of synthetic enzymes that convert cholesterol to active hormones. See your book for the cascades & enzymes Response to release signal is slow and prolonged.
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Non-genomic Actions of Steroids Over the last 10 years, a number of findings indicate that steroids produce rapid (< 10 min) behavioral effect not accounted for by changes in gene expression. e.g. rapid feedback to hypothalmus by corticosterone These findings were the bases of elucidating “non- genomic” effects of steroids which include modulation of channels and neurotransmitter receptors, membrane receptors for steroids, and steroid hormone binding protein receptors.
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