Abstract
We have previously demonstrated that imidazole-4-acetic acid-ribotide (IAA-RP) is present in the mammalian brain and is an endogenous ligand at imidazoline binding sites. In the present study, we used a polyclonal antiserum to visualize IAA-RP-containing neurons in the rat caudoputamen. We observe IAA-RP-immunostained neurons scattered throughout the dorsal and ventral striatum. Most of these cells co-localize GABA, but none are parvalbumin-immunoreactive. In contrast, approximately 50% of the calbindin D28k-immunopositive striatal neurons co-localize IAA-RP. Electrophysiological studies using corticostriatal slices demonstrated that bath application of IAA-RP reversibly depresses the synaptically mediated component of field potentials recorded in the striatum by stimulation of cortical axons. Addition of competitive glutamate receptor antagonists completely blocks the response, confirming its association with glutamatergic transmission. Using paired-pulse stimuli, IAA-RP was shown to exert, at least in part, a presynaptic effect, but blockade of GABAA receptor-mediated transmission did not alter the response. Lastly, we show that this effect is attributable to imidazoline-1 receptors, and not to a2 adrenergic receptors. Since IAA-RP is an endogenous central regulator of blood pressure, and cardiovascular dysfunction is a common symptom associated with Parkinson’s disease (PD), we speculate that IAA-RP-related abnormalities may underlie some of the autonomic dysfunction that occurs in PD.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Alahari, S.K., Lee, J.W., Juliano, R. L. (2000) Nischarin, a novel protein that interacts with the integrin a5 subunit and inhibits cell migration. J. Biol. Chem. 151, 1141–1154.
Artis, A.S., Bozdagi, O., Prell, G.P., Holstein, G.R., Huntley, G.W., Martinelli, G. P. (2007) Endogenous imidazol(in)e receptor ligand modulates corticostriatal synaptic transmission. Soc. Neurosci. Abstr. 893–892.
Barrot, M., Rettori, M. C., Guardiola-Lemaitre, B., Jarry, C., Le Moal, M., Piazza, P. V. (2000) Interactions between imidazoline binding sites and dopamine levels in the rat nucleus accumbens. Eur. J. Neurosci. 12, 4547–4551.
Bousquet, P., Feldman, J., Schwartz, J. (1984) Central cardiovascular effects of a-adrenergic drugs: Difference between catecholamines and imidazolines. J. Pharmacol. Exp. The. 230, 232–236.
Bozdagi, O., Martinelli, G.P., Prell, G.D., Friedrich, V. L. J., Huntley, G.W., Holstein, G. R. (2011) Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of Imidazoline receptors. J. Neurophysiol. in press.
Chan, C. K. S., Burke, S.L., Zhu, H., Piletz, J.E., Head, G. A. (2005) Imidazoline receptors associated with noradrenergic terminals in the rostral ventrolateral medulla mediate the hypotensive responses of moxonidine but not clonidine. Neuroscienc. 132, 991–1007.
Chan, S.L., Morgan, N. G. (1990) Stimulation of insulin secretion by efaroxan may involve interaction with potassium channels. Eur. J. Pharmacol. 176, 97–101.
Cicchetti, F., Prensa, L., Wu, Y., Parent, A. (2000) Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington’s disease. Brain Res. Rev. 34, 80–101.
Crittenden, J. R. and Graybiel, A. M. (2011) Basal ganglia disorders associated with imablances in the striatal striosome and matrix compartments. Front. Neuroanat. 5, 1–25.
Eglen, R.M., Hudson, A.L., Kendall, D.A., Nutt, D.J., Morgan, N.G., Wilson, V.G., Dillon, M. P. (1998) Seeing through a glass darkly: casting light on the imidazoline “I” sites. Trends Pharmacol. Sci. 19, 381–390.
Ernsberger, P., Feinland, G., Meeley, M.P., Reis, D. J. (1990) Characterization and visualization of clonidine-sensitive imidazole sites in rat kidney which recognize clonidine-displacing substance. Am. J. Hypertens. 3, 90–97.
Friedrich, V. L. J., Martinelli, G.P., Prell, G.D., Holstein, G. R. (2007) Distribution and cellular localization of imidazoleacetic acid-ribotide, an endogenous ligand at imidazol(in)e and adrenergic receptors, in rat brain. J. Chem. Neuroanat. 33, 53–64.
Garcia-Sevilla, J.A., Escriba, P.V., Guimon, J. (1990) Imidazoline receptors and human brain disorders. Ann. N.Y. Acad. Sci. 881, 392–309.
Gerfen, C.R., Surmeier, D. J. (2011) Modulation of striatal projection systems by dopamine. Ann. Rev. Neurosci. 1134, 441–466.
Goldstein, D.S., Sewell, L., Sharabi, Y. (2011) Autonomic dysfunction in PD: A window to early detection? J. Neurol. Sci. 310, 118–122.
Ha, A.D., Brown, C.H., York, M.K., Jankovic, J. (2011) The prevalence of symptomatic orthostatic hypotension in patients with Parkinson’s disease and atypical parkinsonism. Parkinsonism Relat. Disor. 17, 625–628.
Halaris, A., Piletz, J. (2007) Agmatine: metabolic pathway and spectrum of activity in brain. CNS Drug. 21, 885–900.
Head, G. A. (1999) Central imidazoline- and a2-receptors involved in the cardiovascular actions of centrally acting antihypertensive agents. Ann. N.Y. Acad. Sci. 881, 279–286.
Head, G.A., Mayorov, D. N. (2006) Imidazoline receptors, novel agents and therapeutic potential. Cardiovas. & Hematol. Agents in Med. Chem. 4, 17–32.
Holstein, G.R., Martinelli, G.P., Friedrich, V. L. J. (2011) Anatomical observations of the caudal vestibulo-sympathetic pathway. J. Vestibular Res. 21, 49–62.
Holstein, G.R., Martinelli, G.P., Henderson, S. C., Friedrich, V. L. J., Rabbitt, R.D., Highstein, S. M. (2004) Gamma-aminobutyric acid is present in a spatially discrete subpopulation of hair cells in the crista ampullaris of the toadfish, Opsanus tau. J. Comp. Neurol. 471, 1–10.
Iodice, V., Low, D.A., Vichayanrat, E., Mathias, C. J. (2011) Cardiovascular autonomic dysfunction in MSA and Parkinson’s disease: Similarities and differences. J. Neurol. Sci. 310, 133–138.
Ivanov, T.R., Jones, J. C, Dontenwill, M., Bousquet, P., Piletz, J. E. (1998) Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera. J. Auton. Nerv. Syst. 72, 98–110.
King, P.R., Gundlach, A.L., Louis, W. J. (1995) Quantitative autoradiographic localization in rat brain of alpha 2-adrenergic and non-adrenergic I-receptor binding sites labelled by [3H]rilmenidine. Brain Res. 675, 264–278.
Li, F., Wu, N., Su, R. B., Chen, Y., Lu, X., Liu, Y., Li, J. (2011) Imidazoline receptor antisera-select-ed/Nischarin regulates the effect of agmatine on the development of morphine dependence. Addiction Biol, (in press).
Makonnen, B., Juntti, N., Larsson, A., Porath, J. (1987) A one-step purification method for monoclonal antibodies based on salt-promoted adsorption chromatography on a thiophilic adsorbent. J. Immunol. Meth. 102, 173–182.
Martinelli, G.P., Friedrich, V. L. J., Prell, G.D., Holstein, G. R. (2007) Vestibular neurons in the rat contain imidazoleacetic acid-ribotide, a putative neurotransmitter involved in blood pressure regulation. J. Comp. Neurol. 501, 568–581.
Matulic-Adamic, J., Watanabe, K. A. (1991) Synthesis of ribosides and ribotides of imidazole-4(5)-acetic acid and l-methylimidazole-4(5)-acetic acid. Kor J. Med Chem. 1, 54–64.
Molderings, G.J., Bõnish, H., Briiss, M., Wolf, C., von Kiigelgen, L., Gõthert, M. (2007) S1P-receptors in PC12 and transfected HEK293 cells: molecular targets of hypotensive imidaoline 1(1) receptor ligands. Neurochem. Int. 51, 476–485.
Morgan, N. G. (1999) Imidazoline receptors: new targets for anti-hyperglycemic drugs. Exp. Opin. Invest. Drug. 8, 575–584.
Parini, A., Moudanos, C.G., Pizzinat, N., Lanier, S. M. (1996) The elusive family of imidazoline binding sites. Trends Pharmacol. Sci. 17, 13–16.
Piletz, J. E, Ivanov, T.R., Sharp, J.D., Ernsberger, P., Chang, C.H., Pickard, R.T., Gold, G., Roth, B., Zhu, H., Jones, J. C., Baldwin, J., Reis, D. J. (2000) Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. DNA Cell. Biol. 19, 319–329.
Prell, G.D., Martinelli, G.P., Holstein, G.R., Matulic-Adamic, J., Watanabe, K.A., Chan, S.L., Morgan, N.G., Haxhiu, M.A., Ernsberger, P. (2004) Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors. Proc. Natl. Acad. Sci. US. 101, 13677–13682.
Reis, D.J., Regunathan, S. (2000) Is agmatine a novel neurotransmitter in brain? Trends inPharmacol. Sei. 21, 187–193.
Smith, K.L., Jessop, D.S., Finn, D. R. (2009) Modulation of stress by imidazoline binding sites: Implications for psychiatric disorders. Stres. 12, 97–114.
Sun, Z., Chang, C.H., Ernsberger, P. (2007) Identification of IRAS/Nischarin as an II-imidazoline receptor in PC12 pheochromocytoma cells. J. Neurochem. 101, 99–108.
Tanabe, M., Kino, Y., Honda, M., Ono, H. (2006) Presynaptic II-Imidazoline receptors reduce GABAergic synaptic transmission in striatal medium spiny neurons. J. Neurosci. 26, 1795–1802.
Velseboer, D. C., de Haan, R.J., Wieling, W., Goldstein, D.S., de Bie, R. M. A. (2011) Prevalence of orthostatic hypotension in Parkinson’s disease: A systematic review and meta-analysis. Parkinsonism Relat. Disord. 17, 724–729.
Wu, N., Su, R.B., Li, J. (2008) Agmatine and imidazoline receptors: Their role in opioid analgesia, tolerance and dependence. CellMol. Neurobiol. 28, 629–641.
Wu, N., Su, R.B., Xu, B. X. Q. L., Liu, Y., Zheng, J.Q., Piletz, J. E., Li, J., Qin, B. Y. (2005) IRAS, a condidate for II-imidazoline receptor, mediates inhibitory effect of agmatine on cellular morphine dependence. Biochem. Pharmacol. 70, 1079–1087.
Ziemssen, T., Reichmann, H. (2010) Cardiovascular autonomic dysfunction in Parkinson’s disease. J. Neurol. Sci. 289, 74–80.
Author information
Authors and Affiliations
Corresponding author
Additional information
Dedicated to Professor József Hámori on the occasion of his 80th birthday
Rights and permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Martir, J.F., Bozdagi, O., Martinelli, G.P. et al. Imidazoleacetic Acid-Ribotide in the Rodent Striatum: A Putative Neurochemical Link Between Motor and Autonomic Deficits in Parkinson’s Disease. BIOLOGIA FUTURA 63 (Suppl 1), 5–18 (2012). https://doi.org/10.1556/ABiol.63.2012.Suppl.1.3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/ABiol.63.2012.Suppl.1.3