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Korea Genome Organization (한국유전체학회)
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Serotonin (5-HT) Receptor Subtypes Mediate Regulation of Neuromodulin Secretion in Rat Hypothalamic Neurons

  • Chin, Chur (Nano-Science Research Division, Korea Institute of Science & Technology) ;
  • Kim, Seong-Il (Nano-Science Research Division, Korea Institute of Science & Technology)
  • Published : 2007.06.30
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Abstract

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.

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References

  1. Arnelo, U., Herrington, M.K., Theodorsson, E., Adrian, T.E., Reidelberger, R., Larsson, J., Marcusson, J., Strommer, J., Ding, X., and Permit, J. (2000). Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain. Brain research 887, 391-398 https://doi.org/10.1016/S0006-8993(00)03070-5
  2. Bonnin,A., Peng, W., Hewlett, W., and Levitt, P. (2006). Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience 141, 781-794 https://doi.org/10.1016/j.neuroscience.2006.04.036
  3. Cai, F., Gyulkhandanyan, A.V., Wheeler, M.B., and Belsham, D.D. (2007). Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin. J. Endocrinol. 192, 605-614 https://doi.org/10.1677/JOE-06-0080
  4. Casoli, T., Di Stefano, G., Gracciotti, N., Fattoretti, P., Solazzi, M., and Bertoni-Freddari, C. (2001). Age-related effects of moderate alcohol consumption on GAP-43 levels in rat hippocampus. Mech. Age. Dev. 122, 1728-1738
  5. Chapman, E.R., Au, D., Alexander, K.A., Nicolson, T.A., and Storm, D.R.(1991). Characterization of the calmodulin binding domain of neuromodulin. Functional significance of serine 41 and phenylalanine 42. J. Biol. Chem. 266, 207-213
  6. Chapman, E.R., Au, D., Alexander, K.A., Nicolson, T.A., and Storm. D.R. (1985). Demonstration of serotoninergic axons terminating on luteinizing hormone-releasing hormone neurons in the preoptic area of the rat using a combination of immunocytochemistry and high resolution autoradiography. Neuroscience 14, 69-78 https://doi.org/10.1016/0306-4522(85)90164-2
  7. Ibarreta, D., Tao, J., Parrilla, R., and Ayruso, M. S. (1997). Mutation analysis of chromosome 19 calmodulin (CALM3) gene in Alzheimer's disease patients. Neuroscience letters 229, 157-160 https://doi.org/10.1016/S0304-3940(97)00453-9
  8. Kim, M.H., Lee, S.H., Park, K.H., Ho, W.K., and Lee, S,H. (2003). Distribution of K+-Dependent Na+/Ca2+ Exchangers in the Rat Supraoptic Magnocellular Neuron Is Polarized to Axon Terminals. J. Neurosci. 23, 11673-11680 https://doi.org/10.1523/JNEUROSCI.23-37-11673.2003
  9. Lee, S.H., Kim, M.H., Park, K.H., Earm, Y.E., and Ho, W.K. (2002). K+-Dependent Na+/$Ca^{2+}$ Exchange Is a Major Ca2+ Clearance Mechanism in Axon Terminals of Rat Neurohypophysis. J. Neurosci. 22, 6891-6899 https://doi.org/10.1523/JNEUROSCI.22-16-06891.2002
  10. Liu, F.Y., Xing, G.G., Qu, X.X., Xu, I.S., Han, J.S., and Wan, Y. (2007). Roles of 5-HT receptor subtypes in the inhibitory effects of 5-HT on C-fiber responses of spinal wide dynamic range neurons in rats. J. Pharmacol. Exp. Ther. 321, 1046-1053 https://doi.org/10.1124/jpet.106.115204
  11. O'Connor, N.A., Paisner, D.A., Huryn, D., and Shea, K.J. (2007). Screening of 5-HT1A receptor antagonists using molecularly imprinted polymer. J. Am. Chem. Soc.129, 1680-1689 https://doi.org/10.1021/ja067276c
  12. Papageorgiou, A. and Denef, C. (2007). Estradiol induces expression of 5-hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 receptor messenger ribonucleic acid in rat anterior pituitary cell aggregates and allows prolactin release via the 5-HT4 receptor. Endocrinology 148, 1384-1395 https://doi.org/10.1210/en.2006-1198
  13. Simler, N., Malgoyre, A., Koulmann, N., Alonso, A., Peinnequin, A., and Bigard, X. (2007). Hypoxic stimulus alters hypothalamic AMP-activated protein kinase phosphorylation concomitant to hypophagia. J. Applied. Physiol. 102, 2135-2141 https://doi.org/10.1152/japplphysiol.01150.2006
  14. Wada, K., Hu, L., Morres, N., Navarro, C.E., Fuda, H., Krsmanovic, L.Z., and Catt, K.J. (2006). Serotonin (5-HT) receptor subtypes mediate specific modes of 5-HT-induced signaling and regulation of neurosecretion in gonadotropinreleasing hormone neurons. Mol. Endocrinology 20, 125-130 https://doi.org/10.1210/me.2005-0109
  15. Xie, J., Dernovici, S., and Ribeiro, P. (2005). Mutagenesis analysis of the serotonin 5-HT2C receptor and a Caenorhabditis elegans 5-HT2 homologue: conserved residues of helix 4 and helix 7 contribute to agonist- dependent activation of 5-HT2 receptors. J. Neurochem. 92, 375-387 https://doi.org/10.1111/j.1471-4159.2004.02867.x