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Purine Club Annual Meeting ABSTRACT BOOK ISTITUTO SUPERIORE DI SANITÀ Purine Club Annual Meeting Istituto Superiore di Sanità Rome, 23-24 September, 2004 ABSTRACT BOOK Edited by Patrizia Popoli (a) and Gloria Cristalli (b) (a) Dipartimento del Farmaco, Istituto Superiore di Sanità, Rome (b) Dipartimento di Scienze Chimiche, Università di Camerino, Camerino ISSN 0393-5620 ISTISAN Congressi 04/C3 Istituto Superiore di Sanità Purine Club Annual Meeting. Istituto Superiore di Sanità. Rome, 23-24 September 2004. Abstract book. Edited by Patrizia Popoli and Gloria Cristalli 2004, vii, 48 p. ISTISAN Congressi 04/C3 The meeting is jointly organized by the Istituto Superiore di Sanità and the Purine Club. The main aim of the annual meetings of the Purine Club is to provide a forum for discussion and to allow collaborations between scientists working in the fields of chemistry, pharmacology and functions of purines. This 2004 meeting includes two authoritative lectures focused on the “fine tuning” by adenosine receptors in the brain and on the regulation of P2X receptors by hypoxia, respectively. The first session of oral communications covers the field of the Central Nervous System effects of purines, while the second one is focused on the pharmacology and functions of P2 receptors. Several other aspects (e.g., synthesis and SAR profile of purine derivatives, expression and functions of P1 and P2 receptors in central and peripheral tissues) are covered as well by the poster session. Key words: Purines, Chemistry, Pharmacology, Functional effects Istituto Superiore di Sanità Riunione annuale Purine Club. Istituto Superiore di Sanità. Roma, 23-24 settembre 2004. Riassunti. A cura di Patrizia Popoli e Gloria Cristalli 2004, vii, 48 p. ISTISAN Congressi 04/C3 (in English) Il convegno è organizzato congiuntamente dall’Istituto Superiore di Sanità e dal Purine Club. L’obiettivo principale dei meeting annuali del Purine Club è quello di favorire gli scambi e di promuovere la collaborazione tra i ricercatori impegnati nello studio della chimica, della farmacologia e degli effetti funzionali delle purine. Questo meeting 2004 comprende due autorevoli letture riguardanti rispettivamente il “fine tuning” esercitato dai recettori dell’adenosina sul sistema nervoso centrale e la regolazione dei recettori P2X da parte di condizioni di ipossia/ischemia. La prima sessione di comunicazioni orali è dedicata agli effetti delle purine sul sistema nervoso centrale, mentre la seconda alla farmacologia ed alle funzioni dei recettori P2. Diversi altri aspetti (come la sintesi ed il profilo struttura-attività dei derivati purinici, o le funzioni dei recettori P1 e P2 a livello centrale e periferico) sono affrontati nell’ambito della sessione poster. Parole chiave: Purine, Chimica, Farmacologia, Effetti funzionali Scientific Committee Gloria Cristalli (Università degli Studi di Camerino), Patrizia Popoli (Istituto Superiore di Sanità) Scientific Secretariat Mariangela Galluzzo, Rosa Grieco (Istituto Superiore di Sanità) Editing: Federica Magnani Per informazioni su questo documento scrivere a: [email protected]. Il rapporto è disponibile online sul sito di questo Istituto: www.iss.it. Presidente dell’Istituto Superiore di Sanità e Direttore responsabile: Enrico Garaci Registro della Stampa - Tribunale di Roma n. 131/88 del 1° marzo 1988 Redazione: Paola De Castro e Sandra Salinetti La responsabilità dei dati scientifici e tecnici è dei singoli autori. © 2004 Istituto Superiore di Sanità (Viale Regina Elena, 299 - 00161 Roma) This meeting and this book are dedicated to the memory of our friend and colleague Stefano Sagratella (1952-2004). We are sure that Stefano, who loved pharmacology and thought us to love it as well, will appreciate to be remembered in such a way. Patrizia Popoli, Claudio Frank, Antonella Pèzzola, Maria Rosaria Domenici, Maria Teresa Tebano, Rosaria Reggio i ii TABLE OF CONTENTS Programme .................................................................................................................. v Lectures How adenosine receptors fine tune neurotransmission to protect the brain ................... 3 Modulation of P2X7 receptor-function by hypoxia/ischemia......................................... 4 First session Receptor-dependent and independent effects of nucleosides in the Central Nervous System....................................................................................... 5 Second session Pharmacology and functions of P2 receptors ................................................................. 13 Poster abstracts ........................................................................................................ 21 Authors’ index ........................................................................................................... 47 iii iv PROGRAMME Tuesday, September 23, 2004 11.00 Registration 13.00 Lunch 14.10 Welcome and opening remarks G. Cristalli, P. Popoli First session RECEPTOR-DEPENDENT AND INDEPENDENT EFFECTS OF NUCLEOSIDES IN THE CENTRAL NERVOUS SYSTEM Chairpersons: M. Morelli, F. Pedata 14.30 Involvement of ERK1/2 phosphorylation in 2-chloro-2’-deoxy-adenosine-induced apoptosis and cell cycle block of human astrocytoma cells S. Ceruti, A. Mazzola, E. Beltrami, M.P. Abbracchio 14.50 Short-term regulation of A2B adenosine receptor functioning by tumor necrosis factor alpha in human astroglial cells M.L. Trincavelli, D. Tuscano, I. Tonazzini, S. Ceruti, M.P. Abbracchio, A. Lucacchini, C. Martini 15.10 Adenosine A2A antagonists and Parkinson’s disease: new findings on parkinsonian tremor N. Simola, A.R. Carta, E. Tronci, A. Pinna, M. Morelli 15.30 Adenosine A2A receptors enable metabotropic glutamate 5 receptors (mGlu5R)-mediated effects in the rodent hippocampus M.R. Domenici, M.T. Tebano, A. Martire, R. Pepponi, J.F. Chen, M.A. Schwarzschild, M.C. Grò, P. Popoli 15.50 The role of adenosine A3 receptors during mild and severe “ischemic conditions” in rat hippocampal slices A. M. Pugliese, E. Coppi, R. Corradetti, F. Pedata 16.10 Coffee break v 16.30 Lecture How adenosine receptors fine tune neurotransmission to protect the brain J.A. Ribeiro Introduced by P. Popoli 17.30 Poster viewing 18.30 Assembly of the Society members 20.30 Social dinner Friday, September 24, 2004 Second Session PHARMACOLOGY AND FUNCTIONS OF P2 RECEPTORS Chairpersons: M.P. Abbracchio, F. Caciagli 9.00 P2Y4 receptor, from differentiation to death F. Cavaliere, S. Amadio, V. Nestola, N. D’Ambrosi , G. Sancesario, G. Bernardi, C. Volonté 9.20 P2Y1 receptor activation regulates oligodendrocytes progenitor migration and proliferation C. Agresti, M.E. Meomartini, S. Amadio, E. Ambrosiani, B. Serafini, C. Volonté, F. Aloisi, S. Visentin 9.40 Upregulation of ionophoric P2X6 in chronic heart failure: interaction with TNF-Į and potential role in myocardial cell death S. Ferrario, C. Banfi, O. De Vincenti, S. Ceruti, M. Fumagalli, A. Mazzola, N. D’Ambrosi, C. Volonté, P. Fratto, E. Vitali, A. Parolari, G. Polvani, P. Biglioli, E. Tremoli, M.P. Abbracchio 10.00 2-Alkynyladenosine phosphates as new ligands for the P2 platelet receptors S. Vittori, S. Costanzi, F. R. Portino, S. Taffi, R. Volpini, M. Cattaneo, G. Cristalli 10.20 Cloning, pharmacological characterization and distribution of the rat G-protein-coupled P2Y13 receptor M. Fumagalli, L. Trincavelli, D. Lecca, C. Martini, P. Ciana, M.P. Abbracchio 10.40 Coffee break vi 11.00 Lecture Modulation of P2X7 receptor function by hypoxia P. Illes Introduced by R. Ciccarelli 11.30 Discussion of posters 1-12 Chairpersons: F. Laghi-Pasini, S. Vittori, C. Volonté 12.30 Lunch 13.30 Discussion of posters 13-24 Chairpersons: R. Ciccarelli, C. Martini, M.T. Tebano 14.30 Concluding remarks G. Cristalli vii viii Lectures 1 2 HOW ADENOSINE RECEPTORS FINE TUNE NEUROTRANSMISSION TO PROTECT THE BRAIN Joaquim Alexandre Ribeiro Laboratory of Neurosciences and Institute of Pharmacology, IMM, Faculty of Medicine, University of Lisboa, Lisboa, Portugal Adenosine is released from insulted neurones and glial cells (1), and is consensually recognised as very important in the homeostasis of the cells, being once named “a signal of life”. It modulates the activity of the nervous system by acting pre- (by inhibiting or facilitating transmitter release), post-, and/or non-synaptically, through activation of physiologically important high affinity adenosine receptors (A1, A2A) as well as of a lower affinity receptors (A2B, A3), which might be relevant in pathological conditions. Adenosine uses very subtle manners to participate in these actions, it acts as a fine tuner between its own receptors and the receptors for other synaptic mediators. From these modulatory actions it is possible to anticipate potential therapeutic applications (e.g. 2), especially when these actions are mediated by high-affinity adenosine A2A receptors in regions where clear functions for this receptor have been identified. The A2A receptor is highly expressed in the striatopallidal GABAergic neurones and expressed in lower levels in other brain regions. A2B possesses low levels of expression in the brain. A3 has apparently intermediate levels of expression in the human cerebellum and hippocampus and low levels in most of the brain. The well known striatal A2A/D2 receptor interactions may offer new therapeutic basis for basal ganglia disorders, such as Parkinson’s disease and Huntington’s chorea, as well as for schizophrenia. Inhibition of D2 receptors in the ventral striatum seems to be associated with the antipsychotic effect of neuroleptics, while inhibition of dopamine
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