 | Edson X. Albuquerque,
M.D., Ph.D.
Professor
Chairman
Department of Pharmacology and Experimental Therapeutics
School of Medicine
4l0-706-7333
ealbuque@umaryland.edu
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ResearchNicotinic and glutamatergic synapses in the mammalian central nervous system (CNS) are known to be involved in cognition, learning, and memory, as well as several pathological conditions, e.g. Alzheimer's disease and epilepsy. Nicotinic receptors are known to play a key role in the control of neuronal function in the hippocampus and many other brain areas. Studies carried out in our laboratory have been directed at characterizing the diversity, ontogenesis, function, and pharmacological properties of nicotinic receptors in the CNS. Toward these aims we have applied different modalities of the patch-clamp technique to hippocampal neurons, in cultures, in brain slices or acutely dissociated, and to cell lines expressing different receptor subtypes.
Studies of the effects of different toxicants, including the heavy metal lead and of organophosphorus compounds, including nerve agents and insecticides, on neuronal functions in vitro and in vivo are also an important part of our ongoing research
Studies of neuronal nicotinic receptors have been rather complex. Based on the analysis of nicotinic whole-cell currents evoked in hippocampal neurons, we have learned that at least three types of nicotinic receptors can be expressed in these neurons: (i) alpha-BGT-sensitive nAChRs, which may bear the alpha7 nAChR subunit; (ii) mecamylamine-sensitive nAChRs, which may be composed of the nAChR-subunit combination alpha3beta2; and (iii) dihydro-beta-erythroidine sensitive nAChRs, which may be made up of the nAChR-subunit combination alpha4beta2. We have demonstrated that the most predominant subtype of neuronal nAChR expressed in hippocampal neurons is highly sensitive to alpha-bungarotoxin, has low affinity for ACh, and desensitizes extremely rapidly. So far, using a system of fast drug delivery that had to be developed to analyze properly the fast kinetic properties of this receptor, we have obtained evidence suggesting that this receptor type may be involved in processes in which a sharp increase in the intracellular concentrations of calcium plays a key role.
We have provided evidence for the existence of endogenous modulators of nicotinic receptor activity in different areas of the brain. Our research has also laid the groundwork for the development of a new class of drugs for treatment of Alzheimer's disease - the so-called "nicotinic allosteric potentiating ligands, of which galantamine is the prototype.
Research in the laboratory continues to have a largely translational component to aid in the development of potential treatments for neuropathological conditions that afflict millions worldwide.
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Lab TechniquesElectrophysiological recording (whole cell and single channel patch clamp) from hippocampal neurons (in cultures, in slices or acutely dissociated); infrared-assisted videomicroscopy coupled with computerized micromanipulators; organotypic cultures of hippocampal slices and septum-hippocampal co-cultures.
PublicationsAlkondon M, Albuquerque EX. Subtype-specific inhibition of nicotinic acetylcholine receptors by choline: a regulatory pathway. J Pharmacol Exp Ther 318:268-275, 2006.
Santos HR, Ribeiro HS, Setti-Perdigao P, Albuquerque EX, Castro NG. The magnitude of alpha7 nicotinic receptor currents in rat hippocampal neurons is dependent upon GABAergic activity and depolarization. J Pharmacol Exp Ther 319:376-85, 2006.
Albuquerque EX, Pereira EFR, Aracava Y, Fawcett WP, Oliveira M, Randall WR, Hamilton TA, Kan RK, Romano Jr. JA, Adler M. Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents. Proc Natl Acad Sci USA, 103:13220-13225, 2006.
Guidetti P, Hoffman GE, Melendez-Ferro M, Albuquerque EX, Schwarcz R. Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia 55:78-92, 2007.
Popa RV, Pereira EF, Lopes C, Maelicke A, Albuquerque EX. The N-butylcarbamate derivative of galantamine acts as an allosteric potentiating ligand on alpha7 nicotinic receptors in hippocampal neurons: clinical implications for treatment of Alzheimer's disease. J Mol Neurosci. 30:227-32, 2006.
Alkondon M, Pereira EF, Potter MC, Kauffman FC, Schwarcz R, Albuquerque EX. Strain-specific nicotinic modulation of glutamatergic transmission in the CA1 field of the rat hippocampus: August Copenhagen Irish versus Sprague-Dawley. J Neurophysiol. 97:1163-70, 2007.
Lopes C, Pereira EF, Wu HQ, Puranik P, Njar V, Schwarcz R, Albuquerque EX. Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at alpha7* nicotinic receptors. J Pharmacol Exp Ther 322:48-58, 2007.
Personal HistoryDr. Edson Xavier de Albuquerque, born in Recife, Pernambuco, Brazil, earned his M.D. degree from the Sch.Med., Fed. Univ. of Pernambuco in 1959, and earned his Ph.D. degree summa cum laude in Physiol. Pharmacol. from the Dept. of Biochem., Biophys. & Pharmacol. at the "Escola Paulista de Medicina" in Sao Paulo, Brazil in 1962. Postdoctoral studies followed at Tulane University, supported by the Rockefellar Foundation, at the Univ. Illinois under the guidance of Prof. Klaus Unna, and at the Univ. Lund (Sweden) with Dr. Stephen Thesleff, at the Karolinska Inst. in Stockholm with Dr. David Ottoson, and at the Dept. of Anatomy at Umea with Dr. Ebba Cedergren.
In 1968, he was offered an Honor Position as a Buswell Fellow at the Univ. Buffalo to join the active group of Sir John Eccles, Prof. Eric Barnard and Prof. David Triggle. He established his own laboratory, developed a number of fundamental studies in the field of neuromuscular transmission, and discovered the properties of many toxins which are used as tools for the characterization of the function of nicotinic receptors in the neuromuscular junction. He was promoted rapidly, receiving by 1972 the position of Prof., and by 1973, Prof. Acting Chair of Pharmacology.
In 1974, Dr. Albuquerque accepted the post of Professor & Chair of the Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore. There he established his laboratory for electrophysiological studies of synaptic transmission and developed the department, which grew from an anonymous department of cell biology to one internationally recognized for its excellence and bringing in a very high level of research funding.
Dr. Albuquerque has received international recognition for his electrophysiological research on neurotransmitter receptors in the central and peripheral nervous systems, including the the Order of the Grand Cross and the Rio Branco Award from Brazil, and in the United States, from the NIH the prestigious Jacob Javits Award Neuroscience Research Award and the Otto Krayer Award from the American Society for Pharmacology and Experimental Therapeutics. Laboratory PersonnelMs. Miriam Akkerman, Research Assistant
Dr. Elena Alexandrova, Postdoctoral Fellow
Mrs. Bhagavathy Alkondon, Laboratory helper
Dr. Manickavasagom Alkondon, Assistant Professor
Dr. Yasco Aracava, Postdoctoral Fellow
Ms. Iusta Caminha, PhD student
Dr. William P. Fawcett, Postdoctoral Fellow
Dr. Edward Helal-Neto, Postdoctoral Fellow
Ms. Rafaela Helal, Research Associate
Dr. Sergei Karnup, Assistant Professor
Mr. Girish Kulkarny, PhD student
Dr. Jacek Mamczarz, Postdoctoral Fellow
Mr. Daniel Nagode, PhD student
Dr. Edna Pereira, Assistant Professor
Ms. Mabel Zelle, Research Assistant
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