Browse > Article

Effects of Somatostatin on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in the Adult Mice  

Park, Seon-Ah (Department of Oral Physiology & Institute of Oral Bioscience, School of Dentistry & BK21 Project, Chonbuk National University)
Yin, Hua (Department of Oral Physiology & Institute of Oral Bioscience, School of Dentistry & BK21 Project, Chonbuk National University)
Bhattarai, Janardhan P. (Department of Oral Physiology & Institute of Oral Bioscience, School of Dentistry & BK21 Project, Chonbuk National University)
Park, Soo-Joung (Department of Oral Physiology & Institute of Oral Bioscience, School of Dentistry & BK21 Project, Chonbuk National University)
Han, Seong-Kyu (Department of Oral Physiology & Institute of Oral Bioscience, School of Dentistry & BK21 Project, Chonbuk National University)
Publication Information
International Journal of Oral Biology / v.34, no.4, 2009 , pp. 191-197 More about this Journal
Abstract
Somatostatin (SST) is a known neuromodulator of the central nervous system. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives many thinmyelinated $A{\delta}$-fiber and unmyelinated C primary afferent fibers and is involved in nociceptive processing. Many studies have demonstrated that SST plays a pivotal role in pain modulation in the spinal cord. However, little is yet known about the direct effects of SST on the SG neurons of the Vc in adult mice. In our present study, we investigated the direct membrane effects of SST and a type 2 SST receptor agonist, seglitide (SEG), on the SG neurons of the Vc using a gramicidin-perforated current clamp in adult mice. The majority (53%, n = 27/51) of the adult SG neurons were hyperpolarized by SST (300 nM) but no differences were found in the hyperpolarization response rate between males and females. When SST was applied successively, the second response was smaller ($76{\pm}9.5%$, n=19), suggesting that SST receptors are desensitized by repeated application. SST-induced hyperpolarization was also maintained under conditions where presynaptic events were blocked ($75{\pm}1.0%$, n=5), suggesting that this neuromodulator exerts direct effects upon postsynaptic SG neurons. SEG was further found to induce membrane hyperpolarization of the SG neurons of the Vc. These results collectively demonstrate that SST inhibits the SG neuronal activities of the Vc in adult mice with no gender bias, and that these effects are mediated via a type 2 SST receptor, suggesting that this is a potential target for orofacial pain modulation.
Keywords
somatostatin; substantia gelatinosa; trigeminal brainstem subnucleus caudalis; gramicidin perforated patch clamp;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bereiter DA. Morphine and somatostatin analogue reduce cfos expression in trigeminal subnucleus caudalis produced by corneal stimulation in the rat. Neuroscience. 1997;77:863-74   DOI   ScienceOn
2 B$\ddot{o}$hm SK, Grady EF, Bunnett NW. Regulatory mechanisms that modulate signalling by G-protein-coupled receptors. Biochem J. 1997;322:1-18   DOI   ScienceOn
3 Horie K, Insel PA. Retrovirally mediated transfer of a G protein-coupled receptor kinase (GRK) dominant-negative mutant enhances endogenous calcitonin receptor signaling in Chinese hamster ovary cells. GRK inhibition enhances expression of receptors and receptor mRNA. J Biol Chem. 2000;275:29433-40   DOI   ScienceOn
4 Ichikawa H, Schulz S, H$\ddot{o}$llt V, Sugimoto T. The somatostatin sst2A receptor in the rat trigeminal ganglion. Neuroscience. 2003;120:807-13   DOI   ScienceOn
5 Krisch B. Somatostatin-immunoreactive fiber projections into the brain stem and the spinal cord of the rat. Cell Tissue Res. 1981;217:531-52   DOI   ScienceOn
6 Reed DK, Korytko AI, Hipkin RW, Wehrenberg WB, Schonbrunn A, Cuttler L. Pituitary somatostatin receptor (sst)1-5 expression during rat development: age-dependent expression of sst2. Endocrinology. 1999;140:4739-44   DOI   ScienceOn
7 Sessle BJ. Mechanisms of trigeminal and occipital pain. Pain Rev. 1996;3:91–116   ScienceOn
8 Shim EY, Kim HJ, Kim MJ, Rhie DJ, Jo YH, Kim MS, Hahn SJ, Lee MY, Yoon SH. Desensitization of somatostatininduced inhibition of low extracellular magnesium concentration-induced calcium spikes in cultured rat hippocampal neurons. Brain Res. 2006;1111:61-71   DOI   ScienceOn
9 Shimon I, Yan X, Taylor JE, Weiss MH, Culler MD, Melmed S. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest. 1997;100:2386-92   DOI   ScienceOn
10 Yin H, Lee KE, Park SA, Bhattarai JP, Suh BJ, Jeon JG, Kim BG, Park SJ, Han SK. Inhibitory effects of somatostatin on the substantia gelatinosa neurons of trigeminal subnucleus caudalis via somatostatin type 2 receptors in juvenile mice. Brain Res. in press, 2009   DOI   ScienceOn
11 Holliday ND, Tough IR, Cox HM. A functional comparison of recombinant and native somatostatin sst2 receptor variants in epithelia. Br J Pharmacol. 2007;152:132-40   DOI   ScienceOn
12 Moore SD, Madamba, SG, Jo$\ddot{e}$ls M, Siggins GR. Somatostatin augments the M-current in hippocampal neurons. Science. 1998;239:278-80   DOI   ScienceOn
13 Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol. 1999;20:157-98   DOI   ScienceOn
14 Lefkowitz RJ. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem. 1998;273:18677-80   DOI   ScienceOn
15 Takeda M, Kadoi J, Takahashi M, Nasu M, Matsumoto S. Somatostatin inhibits the excitability of rat small-diameter trigeminal ganglion neurons that innervate nasal mucosa and project to the upper cervical dorsal horn via activation of somatostatin 2a receptor. Neuroscience. 2007;148:44-756   DOI   ScienceOn
16 Premont RT, Inglese J, Lefkowitz RJ. Protein kinases that phosphorylate activated G protein-coupled receptors. FASEB J. 1995;9:175-82   DOI   ScienceOn
17 Pittman QJ, Siggins GR. Somatostatin hyperpolarizes hippocampal pyramidal cells in vitro. Brain Res. 1981;221:402-8   DOI   ScienceOn
18 Lahlou H, Guillermet J, Hortala M, Vernejoul F, Pyronnet S, Bousquet C, Susini C. Molecular signaling of somatostatin receptors. Ann N Y Acad Sci. 2004;1014:121-31   DOI   ScienceOn
19 Li YQ, Li H, Kaneko T, Mizuno N. Substantia gelatinosa neurons in the medullary dorsal horn: An intracellular labeling study in the rat. J Comp Neurol. 1999; 411:399-412   DOI   ScienceOn
20 Tessler A, Himes BT, Gruber-Bollinger J, Reichlin S. Characterization of forms of immunoreactive somatostatin in sensory neuron and normal and deafferented spinal cord. Brain Res. 1986;370:232-40   DOI   ScienceOn
21 Wang HL, Dichter M, Reisine T. Lack of cross-desensitization of somatostatin-14 and somatostatin-28 receptors coupled to potassium channels in rat neocortical neurons. Mol Pharmacol. 1990;38:357-61   ScienceOn
22 Mollenholt P, Rawal N, Gordh TJr, Olsson Y. Intrathecal and epidural somatostatin for patients with cancer. Analgesic effects and postmortem neuropathologic investigations of spinal cord and nerve roots. Anesthesiology. 1994;81:531-3   DOI   ScienceOn
23 Epelbaum J, Dournaud P, Fodor M, Viollet C. The neurobiology of somatostatin. Crit Rev Neurobiol. 1994;8:25-44   ScienceOn
24 Rapacciuolo A, Suvarna S, Barki-Harrington L, Luttrell LM, Cong M, Lefkowitz RJ, Rockman HA. Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways. J Biol Chem. 2003;278:35403-11   DOI   ScienceOn
25 Schindler M, Humphrey PP, Emson PC. Somatostatin receptors in the central nervous system. Prog Neurobiol. 1996;50:9-47   DOI   ScienceOn
26 Schonbrunn A, Gu YZ, Dournard P, Beaudet A, Tannenbaum GS, Brown PJ. Somatostatin receptor subtypes: specific expression and signaling properties. Metabolism. 1996;45:8-11   DOI   ScienceOn
27 Yoon SH, Jin W, Spencer RJ, Loh HH, and Thayer SA. Desensitization of delta-opioid-induced mobilization of $Ca^{2+}$ stores in NG108-15 cells. Brain Res. 1998;802:9-18   DOI   ScienceOn
28 Kramer HK, Simon EJ. Role of protein kinase C (PKC) in agonist-induced mu-opioid receptor down-regulation: I. PKC translocation to the membrane of SH-SY5Y neuroblastoma cells is induced by mu-opioid agonists. J Neurochem. 72(2):585-593, 1999   DOI   ScienceOn
29 Han SK, Todman MG, Herbison AE. Endogenous GABA release inhibits the firing of adult gonadotropin releasing hormone neurons. Endocrinology. 2004;145:495-9   DOI   ScienceOn
30 Rhee JS, Ebihara S, Akaike N. Gramicidin perforated patchclamp technique reveals glycine-gated outward chloride current in dissociated nucleus solitari neurons of the rat. J Neurophysiol. 1994;72:1103-8   DOI   ScienceOn
31 Jiang N, Furue H, Katafuchi T, Yoshimura, M. Somatostatin directly inhibits substantia gelatinosa neurons in adult rat spinal dorsal horn in vitro. Neurosci Res. 2003;47:97-107   DOI   ScienceOn
32 Nakatsuka T, Fujita T, Inoue K, Kumamoto E. Activation of GIRK channels in substantia gelatinosa neurones of the adult rat spinal cord: a possible involvement of somatostatin. J Physiol. 2008;586:2511-22   DOI   ScienceOn
33 Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PP, O'Carroll, AM, Patel YC, Schonbrunn A, Taylor JE, Reisine T. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci. 1995;16:86-8   DOI   ScienceOn