Table of Contents
International Journal of Peptides
Volume 2010, Article ID 616757, 8 pages
http://dx.doi.org/10.1155/2010/616757
Review Article

Ghrelin: Central Nervous System Sites of Action in Regulation of Energy Balance

1Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2
2Department of Physiology, Queen's University, Kingston, ON, Canada K7L 3N6

Received 31 October 2009; Accepted 8 December 2009

Academic Editor: Alessandro Laviano

Copyright © 2010 Mark Fry and Alastair V. Ferguson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa, “Ghrelin is a growth-hormone-releasing acylated peptide from stomach,” Nature, vol. 402, no. 6762, pp. 656–660, 1999. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Tschop, D. L. Smiley, and M. L. Heiman, “Ghrelin induces adiposity in rodents,” Nature, vol. 407, no. 6806, pp. 908–913, 2000. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Okada, S. Ishii, S. Minami, H. Sugihara, T. Shibasaki, and I. Wakabayashi, “Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats,” Endocrinology, vol. 137, no. 11, pp. 5155–5158, 1996. View at Publisher · View at Google Scholar · View at Scopus
  4. S. L. Dickson and S. M. Luckman, “Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6,” Endocrinology, vol. 138, no. 2, pp. 771–777, 1997. View at Publisher · View at Google Scholar · View at Scopus
  5. M. G. Willesen, P. Kristensen, and J. Romer, “Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat,” Neuroendocrinology, vol. 70, no. 5, pp. 306–316, 1999. View at Google Scholar · View at Scopus
  6. M. A. Cowley, R. G. Smith, S. Diano et al., “The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis,” Neuron, vol. 37, no. 4, pp. 649–661, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. J. P. Camina, “Cell biology of the ghrelin receptor,” Journal of Neuroendocrinology, vol. 18, no. 1, pp. 65–76, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Katayama, H. Nogami, J. Nishiyama, T. Kawase, and K. Kawamura, “Developmentally and regionally regulated expression of growth hormone secretagogue receptor mRNA in rat brain and pituitary gland,” Neuroendocrinology, vol. 72, pp. 333–340, 2000. View at Google Scholar
  9. J. M. Zigman, J. E. Jones, C. E. Lee, C. B. Saper, and J. K. Elmquist, “Expression of ghrelin receptor mRNA in the rat and the mouse brain,” Journal of Comparative Neurology, vol. 494, no. 3, pp. 528–548, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. A. D. Howard, S. D. Feighner, D. F. Cully et al., “A receptor in pituitary and hypothalamus that functions in growth hormone release,” Science, vol. 273, no. 5277, pp. 974–977, 1996. View at Google Scholar · View at Scopus
  11. P. A. Bennett, G. B. Thomas, A. D. Howard et al., “Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated by growth hormone in the rat,” Endocrinology, vol. 138, no. 11, pp. 4552–4557, 1997. View at Publisher · View at Google Scholar · View at Scopus
  12. X.-M. Guan, H. Yu, O. C. Palyha et al., “Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues,” Molecular Brain Research, vol. 48, no. 1, pp. 23–29, 1997. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Asakawa, A. Inui, T. Kaga et al., “Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin,” Gastroenterology, vol. 120, no. 2, pp. 337–345, 2001. View at Google Scholar · View at Scopus
  14. M. Bagnasco, G. Tulipano, M. R. Melis, A. Argiolas, D. Cocchi, and E. E. Muller, “Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting,” Regulatory Peptides, vol. 111, no. 1–3, pp. 161–167, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. A. M. Wren, C. J. Small, C. R. Abbott et al., “Ghrelin causes hyperphagia and obesity in rats,” Diabetes, vol. 50, no. 7–12, pp. 2540–2547, 2001. View at Google Scholar · View at Scopus
  16. M. Nakazato, N. Murakami, Y. Date et al., “A role for ghrelin in the central regulation of feeding,” Nature, vol. 409, no. 6817, pp. 194–198, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. P. K. Olszewski, M. K. Grace, C. J. Billington, and A. S. Levine, “Hypothalamic paraventricular injections of ghrelin: effect on feeding and c-Fos immunoreactivity,” Peptides, vol. 24, no. 6, pp. 919–923, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. C. B. Lawrence, A. C. Snape, F. M.-H. Baudoin, and S. M. Luckman, “Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers,” Endocrinology, vol. 143, no. 1, pp. 155–162, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. M. S. Mondal, Y. Date, H. Yamaguchi et al., “Identification of ghrelin and its receptor in neurons of the rat arcuate nucleus,” Regulatory Peptides, vol. 126, no. 1-2, pp. 55–59, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. M. van den Top, K. Lee, A. D. Whyment, A. M. Blanks, and D. Spanswick, “Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus,” Nature Neuroscience, vol. 7, no. 5, pp. 493–494, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. A. N. van den Pol, Y. Yao, L.-Y. Fu et al., “Neuromedin B and Gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons,” Journal of Neuroscience, vol. 29, no. 14, pp. 4622–4639, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Kohno, H.-Z. Gao, S. Muroya, S. Kikuyama, and T. Yada, “Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin,” Diabetes, vol. 52, no. 4, pp. 948–956, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Riediger, M. Traebert, H. A. Schmid, C. Scheel, T. A. Lutz, and E. Scharrer, “Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus,” Neuroscience Letters, vol. 341, no. 2, pp. 151–155, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Tamura, J. Kamegai, T. Shimizu, S. Ishii, H. Sugihara, and S. Oikawa, “Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats,” Endocrinology, vol. 143, no. 9, pp. 3268–3275, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Bugarith, T. T. Dinh, A.-J. Li, R. C. Speth, and S. Ritter, “Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake,” Endocrinology, vol. 146, no. 3, pp. 1179–1191, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. H. Y. Chen, M. E. Trumbauer, A. S. Chen et al., “Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein,” Endocrinology, vol. 145, no. 6, pp. 2607–2612, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. A. M. Wren, C. J. Small, H. L. Ward et al., “The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion,” Endocrinology, vol. 141, no. 11, pp. 4325–4328, 2000. View at Google Scholar · View at Scopus
  28. A. M. Wren, L. J. Seal, M. A. Cohen et al., “Ghrelin enhances appetite and increases food intake in humans,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 12, pp. 5992–5995, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. A. K. Hewson and S. L. Dickson, “Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats,” Journal of Neuroendocrinology, vol. 12, no. 11, pp. 1047–1049, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Wang, D. H. Saint-Pierre, and Y. Tache, “Peripheral ghrelin selectively increases Fos expression in neuropeptide Y-synthesizing neurons in mouse hypothalamic arcuate nucleus,” Neuroscience Letters, vol. 325, no. 1, pp. 47–51, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. P. Kobelt, A.-S. Wisser, A. Stengel et al., “Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats,” Brain Research, vol. 1204, pp. 77–86, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Takayama, Y. Johno, K. Hayashi, K. Yakabi, T. Tanaka, and S. Ro, “Expression of c-Fos protein in the brain after intravenous injection of ghrelin in rats,” Neuroscience Letters, vol. 417, no. 3, pp. 292–296, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. S. W. Shaver, J. J. Pang, D. S. Wainman, K. M. Wall, and P. M. Gross, “Morphology and function of capillary networks in subregions of the rat tuber cinereum,” Cell and Tissue Research, vol. 267, no. 3, pp. 437–448, 1992. View at Google Scholar · View at Scopus
  34. J. F. R. Paton, J. Deuchars, Z. Ahmad, L.-F. Wong, D. Murphy, and S. Kasparov, “Adenoviral vector demonstrates that angiotensin II-induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat,” Journal of Physiology, vol. 531, no. 2, pp. 445–458, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. J. F. R. Paton, S. Wang, J. W. Polson, and S. Kasparov, “Signalling across the blood brain barrier by angiotensin II: novel implications for neurogenic hypertension,” Journal of Molecular Medicine, vol. 86, no. 6, pp. 705–710, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. F. S. Gaskin, S. A. Farr, W. A. Banks, V. B. Kumar, and J. E. Morley, “Ghrelin-induced feeding is dependent on nitric oxide,” Peptides, vol. 24, no. 6, pp. 913–918, 2003. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Mueckler, C. Caruso, S. A. Baldwin et al., “Sequence and structure of a human glucose transporter,” Science, vol. 229, no. 4717, pp. 941–945, 1985. View at Google Scholar · View at Scopus
  38. W. A. Banks, “Leptin transport across the blood-brain barrier: implications for the cause and treatment of obesity,” Current Pharmaceutical Design, vol. 7, no. 2, pp. 125–133, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. W. A. Banks, M. Tschop, S. M. Robinson, and M. L. Heiman, “Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure,” Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 2, pp. 822–827, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. W. A. Banks, B. O. Burney, and S. M. Robinson, “Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood-brain barrier,” Peptides, vol. 29, no. 11, pp. 2061–2065, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. W. A. Banks, “The blood-brain barrier: connecting the gut and the brain,” Regulatory Peptides, vol. 149, no. 1–3, pp. 11–14, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. M. A. Bednarek, S. D. Feighner, S.-S. Pong et al., “Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a,” Journal of Medicinal Chemistry, vol. 43, no. 23, pp. 4370–4376, 2000. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Holst, A. Cygankiewicz, T. H. Jensen, M. Ankersen, and T. W. Schwartz, “High constitutive signaling of the ghrelin receptor—identification of a potent inverse agonist,” Molecular Endocrinology, vol. 17, no. 11, pp. 2201–2210, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Fry and A. V. Ferguson, “Ghrelin modulates electrical activity of area postrema neurons,” American Journal of Physiology, vol. 296, no. 3, pp. R485–R492, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. K. J. Pulman, W. M. Fry, G. T. Cottrell, and A. V. Ferguson, “The subfornical organ: a central target for circulating feeding signals,” Journal of Neuroscience, vol. 26, no. 7, pp. 2022–2030, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Kim, K. Nakajima, Y. Oomura, M. J. Wayner, and K. Sasaki, “Electrophysiological effects of ghrelin on pedunculopontine tegmental neurons in rats: an in vitro study,” Peptides, vol. 30, no. 4, pp. 745–757, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. D. Grouselle, E. Chaillou, A. Caraty et al., “Pulsatile cerebrospinal fluid and plasma ghrelin in relation to growth hormone secretion and food intake in the sheep,” Journal of Neuroendocrinology, vol. 20, no. 10, pp. 1138–1146, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra, “Interacting appetite-regulating pathways in the hypothalamic regulation of body weight,” Endocrine Reviews, vol. 20, no. 1, pp. 68–100, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Traebert, T. Riediger, S. Whitebread, E. Scharrer, and H. A. Schmid, “Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus,” Journal of Neuroendocrinology, vol. 14, no. 7, pp. 580–586, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. B. Peruzzo, F. E. Pastor, J. L. Blazquez et al., “A second look at the barriers of the medial basal hypothalamus,” Experimental Brain Research, vol. 132, no. 1, pp. 10–26, 2000. View at Google Scholar · View at Scopus
  51. O. Cheunsuang, A. L. Stewart, and R. Morris, “Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals,” Cell and Tissue Research, vol. 325, no. 2, pp. 397–402, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. O. Cheunsuang and R. Morris, “Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors,” Glia, vol. 52, no. 3, pp. 228–233, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. R. D. Broadwell and M. W. Brightman, “Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood,” Journal of Comparative Neurology, vol. 166, no. 3, pp. 257–283, 1976. View at Google Scholar · View at Scopus
  54. R. D. Broadwell, B. J. Balin, M. Salcman, and R. S. Kaplan, “Brain-blood barrier? Yes and no,” Proceedings of the National Academy of Sciences of the United States of America, vol. 80, no. 23, pp. 7352–7356, 1983. View at Google Scholar · View at Scopus
  55. B. Krisch, H. Leonhardt, and W. Buchheim, “The functional and structural border between the CSF- and blood-milieu in the circumventricular organs (Organum vasculosum laminae terminalis, subfornical organ, area postrema) of the rat,” Cell and Tissue Research, vol. 195, no. 3, pp. 485–497, 1978. View at Google Scholar · View at Scopus
  56. L. M. Maness, A. J. Kastin, and W. A. Banks, “Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1α to the brain,” American Journal of Physiology, vol. 275, no. 2, pp. E207–E212, 1998. View at Google Scholar · View at Scopus
  57. E. E. Jobst, P. J. Enriori, and M. A. Cowley, “The electrophysiology of feeding circuits,” Trends in Endocrinology and Metabolism, vol. 15, no. 10, pp. 488–499, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Date, T. Shimbara, S. Koda et al., “Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus,” Cell Metabolism, vol. 4, no. 4, pp. 323–331, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. P. M. Gross, “Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema,” Canadian Journal of Physiology and Pharmacology, vol. 69, no. 7, pp. 1010–1025, 1991. View at Google Scholar · View at Scopus
  60. M. J. McKinley, R. M. McAllen, P. Davern et al., “The sensory circumventricular organs of the mammalian brain,” Advances in Anatomy, Embryology, and Cell Biology, vol. 172, pp. 3–12, 2003. View at Google Scholar
  61. C. H. Rhodes, J. I. Morrell, and D. W. Pfaff, “Immunohistochemical analysis of magnocellular elements in rat hypothalamus: distribution and numbers of cells containing neurophysin, oxytocin, and vasopressin,” Journal of Comparative Neurology, vol. 198, no. 1, pp. 45–64, 1981. View at Google Scholar · View at Scopus
  62. R. R. Miselis, “The subfornical organ's neural connections and their role in water balance,” Peptides, vol. 3, no. 3, pp. 501–502, 1982. View at Publisher · View at Google Scholar · View at Scopus
  63. R. W. Lind and A. K. Johnson, “Subfornical organ-median preoptic connections and drinking and pressor responses to angiotensin II,” Journal of Neuroscience, vol. 2, no. 8, pp. 1043–1051, 1982. View at Google Scholar · View at Scopus
  64. R. R. Miselis, M. L. Weiss, and R. E. Shapiro, “Modulation of the visceral neuraxis,” in Circumventricular Organs and Body Fluids, P. Gross, Ed., CRC Press, Boca Raton, Fla, USA, 1987. View at Google Scholar
  65. R. W. Lind, “Neural connections,” in Circumventricular Organs and Body Fluids, P. Gross, Ed., pp. 27–42, CRC Press, Boca Raton, Fla, USA, 1987. View at Google Scholar
  66. A. M. Zardetto-Smith and T. S. Gray, “A direct neural project from the nucleus of the solitary tract to the subfornical organ in the rat,” Neuroscience Letters, vol. 80, no. 2, pp. 163–166, 1987. View at Google Scholar · View at Scopus
  67. R. E. Shapiro and R. R. Miselis, “The central neural connections of the area postrema of the rat,” Journal of Comparative Neurology, vol. 234, no. 3, pp. 344–364, 1985. View at Google Scholar · View at Scopus
  68. D. van der Kooy and L. Y. Koda, “Organization of the projections of a circumventricular organ: the area postrema in tha rat,” Journal of Comparative Neurology, vol. 219, no. 3, pp. 328–338, 1983. View at Google Scholar · View at Scopus
  69. R. E. Shapiro and R. R. Miselis, “The central organization of the vagus nerve innervating the stomach of the rat,” Journal of Comparative Neurology, vol. 238, no. 4, pp. 473–488, 1985. View at Google Scholar · View at Scopus
  70. M. Palkovits, L. Zaborszky, A. Feminger et al., “Noradrenergic innervation of the rat hypothalamus: experimental biochemical and electron microscopic studies,” Brain Research, vol. 191, no. 1, pp. 161–171, 1980. View at Publisher · View at Google Scholar · View at Scopus
  71. P. E. Sawchenko, L. W. Swanson, R. Grzanna, P. R. Howe, S. R. Bloom, and J. M. Polak, “Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus,” Journal of Comparative Neurology, vol. 241, no. 2, pp. 138–153, 1985. View at Google Scholar · View at Scopus
  72. P. E. Sawchenko and L. W. Swanson, “Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat,” Journal of Comparative Neurology, vol. 205, no. 3, pp. 260–272, 1982. View at Google Scholar · View at Scopus
  73. J. Guy and G. Pelletier, “Neuronal interactions between neuropeptide Y (NPY) and catecholaminergic systems in the rat arcuate nucleus as shown by dual immunocytochemistry,” Peptides, vol. 9, no. 3, pp. 567–570, 1988. View at Google Scholar · View at Scopus
  74. G. S. Fraley and S. Ritter, “Immunolesion of norepinephrine and epinephrine afferents to medial hypothalamus alters basal and 2-deoxy-D-glucose-induced neuropeptide Y and agouti gene-related protein messenger ribonucleic acid expression in the arcuate nucleus,” Endocrinology, vol. 144, no. 1, pp. 75–83, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. C. B. Saper and A. D. Loewy, “Efferent connections of the parabrachial nucleus in the rat,” Brain Research, vol. 197, no. 2, pp. 291–317, 1980. View at Publisher · View at Google Scholar · View at Scopus
  76. A. V. Ferguson, “Neurophysiological analysis of mechanisms for subfornical organ and area postrema involvement in autonomic control,” Progress in Brain Research, vol. 91, pp. 413–421, 1992. View at Google Scholar · View at Scopus
  77. J. T. Fitzsimons, “Angiotensin, thirst, and sodium appetite,” Physiological Reviews, vol. 78, no. 3, pp. 583–686, 1998. View at Google Scholar · View at Scopus
  78. T. A. Lutz, “Amylinergic control of food intake,” Physiology and Behavior, vol. 89, no. 4, pp. 465–471, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. E. G. Mietlicki, E. L. Nowak, and D. Daniels, “The effect of ghrelin on water intake during dipsogenic conditions,” Physiology and Behavior, vol. 96, no. 1, pp. 37–43, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. H. Hashimoto, H. Otsubo, H. Fujihara et al., “Centrally administered ghrelin potently inhibits water intake induced by angiotensin II and hypovolemia in rats,” Journal of Physiological Sciences, vol. 60, no. 1, pp. 19–25, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Hashimoto, H. Fujihara, M. Kawasaki et al., “Centrally and peripherally administered ghrelin potently inhibits water intake in rats,” Endocrinology, vol. 148, no. 4, pp. 1638–1647, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Fry and A. V. Ferguson, “The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behavior,” Physiology and Behavior, vol. 91, no. 4, pp. 413–423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Fry, T. D. Hoyda, and A. V. Ferguson, “Making sense of it: roles of the sensory circumventricular organs in feeding and regulation of energy homeostasis,” Experimental Biology and Medicine, vol. 232, no. 1, pp. 14–26, 2007. View at Google Scholar · View at Scopus
  84. H. J. Grill, “Distributed neural control of energy balance: contributions from hindbrain and hypothalamus,” Obesity, vol. 14, supplement 5, pp. 216S–221S, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Li, X. Wu, Y. Zhao, S. Chen, and C. Owyang, “Ghrelin acts on the dorsal vagal complex to stimulate pancreatic protein secretion,” American Journal of Physiology, vol. 290, no. 6, pp. G1350–G1358, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Gilg and T. A. Lutz, “The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema,” Physiology and Behavior, vol. 87, no. 2, pp. 353–359, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Arnold, A. Mura, W. Langhans, and N. Geary, “Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat,” Journal of Neuroscience, vol. 26, no. 43, pp. 11052–11060, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. L. F. Faulconbridge, H. J. Grill, J. M. Kaplan, and D. Daniels, “Caudal brainstem delivery of ghrelin induces fos expression in the nucleus of the solitary tract, but not in the arcuate or paraventricular nuclei of the hypothalamus,” Brain Research, vol. 1218, pp. 151–157, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. L. F. Faulconbridge, D. E. Cummings, J. M. Kaplan, and H. J. Grill, “Hyperphagic effects of brainstem ghrelin administration,” Diabetes, vol. 52, no. 9, pp. 2260–2265, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. L. F. Faulconbridge, H. J. Grill, and J. M. Kaplan, “Distinct forebrain and caudal brainstem contributions to the neuropeptide Y mediation of ghrelin hyperphagia,” Diabetes, vol. 54, no. 7, pp. 1985–1993, 2005. View at Publisher · View at Google Scholar · View at Scopus