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Chen, J.-F.; Moratalla, R.; Impagnatiello, F.; Grandy, D.K.; Cuellar, B.; Rubinstein, M.; Beilstein, M.A.; Hackett, E.; Fink, J.S.; Low, M.J.; Ongini, E.; Schwarzschild, M.A. "The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice" (2001) Proceedings of the National Academy of Sciences of the United States of America. 98(4):1970-1975
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Abstract:

The A2AR is largely coexpressed with D2Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A2AR antagonizes D2R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A2AR-D2R interaction. However, whether the D2R is required for the A2AR to exert its neural function is an open question. In this study, we examined the role of D2Rs in A2AR-induced behavioral and cellular responses, by using genetic knockout (KO) models (mice deficient in A2ARs or D2Rs or both). Behavioral analysis shows that the A2AR agonist 2-4-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine reduced spontaneous as well as amphetamine-induced locomotion in both D2 KO and wild-type mice. Conversely, the nonselective adenosine antagonist caffeine and the A2AR antagonist 8-(3-chlorostyryl)caffeine produced motor stimulation in mice lacking the D2R, although the stimulation was significantly attentuated. At the cellular level, A2AR inactivation counteracted the increase in enkephalin expression in striatopallidal neurons caused by D2R deficiency. Consistent with the D2 KO phenotype, A2AR inactivation partially reversed both acute D2R antagonist (haloperidol)-induced catalepsy and chronic haloperidol-induced enkephalin mRNA expression. Together, these results demonstrate that A2ARs elicit behavioral and cellular responses despite either the genetic deficiency or pharmacological blockade of D2Rs. Thus, A2AR-mediated neural functions are partially independent of D2Rs. Moreover, endogenous adenosine acting at striatal A2ARs may be most accurately viewed as a facilitative modulator of striatal neuronal activity rather than simply as an inhibitory modulator of D2R neurotransmission.

Registro:

Documento: Artículo
Título:The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice
Autor:Chen, J.-F.; Moratalla, R.; Impagnatiello, F.; Grandy, D.K.; Cuellar, B.; Rubinstein, M.; Beilstein, M.A.; Hackett, E.; Fink, J.S.; Low, M.J.; Ongini, E.; Schwarzschild, M.A.
Filiación:Molecular Neurobiology Laboratory, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, United States
Cajal Institute, Madrid, 28002, Spain
Schering-Plough Research Institute, Milan 20132, Italy
Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, United States
Department of Physiology Pharmacology, Oregon Health Sciences University, Portland, OR 97201, United States
INGEBI, Department of Biological Science, University of Buenos Aires, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Department of Neurology, Boston University, School of Medicine, Boston, MA 02118, United States
Palabras clave:8 (3 chlorostyryl)caffeine; adenosine A2a receptor; adenosine A2a receptor agonist; adenosine A2a receptor antagonist; adenosine receptor blocking agent; amphetamine derivative; caffeine; dopamine 2 receptor; dopamine 2 receptor blocking agent; enkephalin; haloperidol; animal behavior; animal experiment; animal model; article; controlled study; dopaminergic activity; drug effect; knockout mouse; locomotion; motor activity; mouse; nerve conduction; neurotransmission; nonhuman; priority journal; protein expression; receptor down regulation; Adenosine; Amphetamines; Animals; Caffeine; Catalepsy; Corpus Striatum; Dopamine Antagonists; Enkephalins; Gene Expression; Haloperidol; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Phenethylamines; Receptor, Adenosine A2A; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Purinergic P1; RNA, Messenger; Animalia
Año:2001
Volumen:98
Número:4
Página de inicio:1970
Página de fin:1975
DOI: http://dx.doi.org/10.1073/pnas.98.4.1970
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:8-(3-chlorostyryl)caffeine, 148589-13-3; Adenosine, 58-61-7; Amphetamines; Caffeine, 58-08-2; CGS 21680, 120225-54-9; Dopamine Antagonists; Enkephalins; Haloperidol, 52-86-8; Phenethylamines; Receptor, Adenosine A2A; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Purinergic P1; RNA, Messenger
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v98_n4_p1970_Chen

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Citas:

---------- APA ----------
Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D.K., Cuellar, B., Rubinstein, M., Beilstein, M.A.,..., Schwarzschild, M.A. (2001) . The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 98(4), 1970-1975.
http://dx.doi.org/10.1073/pnas.98.4.1970
---------- CHICAGO ----------
Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D.K., Cuellar, B., Rubinstein, M., et al. "The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice" . Proceedings of the National Academy of Sciences of the United States of America 98, no. 4 (2001) : 1970-1975.
http://dx.doi.org/10.1073/pnas.98.4.1970
---------- MLA ----------
Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D.K., Cuellar, B., Rubinstein, M., et al. "The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice" . Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 4, 2001, pp. 1970-1975.
http://dx.doi.org/10.1073/pnas.98.4.1970
---------- VANCOUVER ----------
Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D.K., Cuellar, B., Rubinstein, M., et al. The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice. Proc. Natl. Acad. Sci. U. S. A. 2001;98(4):1970-1975.
http://dx.doi.org/10.1073/pnas.98.4.1970