Sistema cannabinoide endógeno: ligandos y receptores acoplados a mecanismos de transducción de señales

Autores/as

  • J. A. Ramos Atance Instituto Universitario de Drogodependencias, Departamento de Bioquímica y Biología Molecular, acultad de Medicina, Universidad Complutense.
  • J. Fernández Ruiz Instituto Universitario de Drogodependencias, Departamento de Bioquímica y Biología Molecular, acultad de Medicina, Universidad Complutense.

DOI:

https://doi.org/10.20882/adicciones.672

Palabras clave:

endocannabinoides, anandamida, receptores CB1 y CB2, transducción de señales, neurotransmisores, cannabis

Resumen

Numerosos estudios realizados en las dos últimas décadas han demostrado la existencia en el organismo animal de un sistema cannabinoide endógeno, constituido por unos ligandos, los endocannabinoides. Se han descrito dos tipos de receptores para cannabinoides: los denominados CB1, localizados preferentemente en cerebro y los CB2 que están localizados en el sistema inmune. Los dos endocannabinoides de los que más datos se dispone son la araquidoniletanolamida o anandamida y el 2-araquidonilglicerol, habiéndose postulado su posible actuación como neurotransmisores o neuromoduladores. La distribución cerebral de los endocannabinoides y de los receptores CB1 ha permitido conocer las funciones fisiológicas en las que está involucrado este sistema. Participa, a través de modular la actividad de los neurotransmisores, en la regulación del comportamiento motor y de la secreción de hormonas adenohipofisarias, interacciona con la dopamina y con el GABA, mientras que, en el caso de la memoria y el aprendizaje, lo hace con el GABA y el glutamato. La dopamina y los péptidos opioides podrían estar implicados en la participación de los endocannabinoides en el sistema de recompensa y en el control de la nocicepción. Por otro lado, la síntesis de anandamida, en condiciones de isquemia, podría jugar un papel protector en las regiones cerebrales afectadas. Se ha visto que este compuesto inhibe la captación mitocondrial de calcio y la liberación de glutamato, efectos ámbos que contribuyen a la citotoxicidad cerebral. 

Citas

Aceto M.D., Scates S.M., Lowe J.A., Martin B.R. (1995) Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. Eur. J. Pharmacol. 282:R1-R2.

Bachur NR., Masek K., Melmon KL., Udenfriend S. (1995) Fatty acid amides of ethanolamine in mammalian tissues J. Biol Chem 240:1019-1024.

Beltramo M., Stella N., Calignano A., Lin S.Y., Makriyannis A., Piomelli D. (1997) Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277: 1094-1097.

Ben-Shabat S., Fride E., Sheskin T., Tamiri T., Rhee M.H., Vogel Z., Bisogno T., De Petrocellis L., Di Marzo V., Mechoulam R. (1998) Eur. J. Pharmacol. 353:23-31.

Berrendero F., García L., Hernández M.L., Romero J., Cebeira M., deMiguel R., Ramos J.A., Fernandez-Ruiz J.J., (1998) Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development 125:3179-3188.

Berrendero F., Sepe N., Ramos J.A., Di Marzo V., Fernandez-Ruiz J.J. (1999) Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 33:181-191.

Bisogno T., Berrendero F., Ambrosino G., Cebeira M., Ramos J.A., Fernandez-Ruiz J.J., Di Marzo V. (1999) Brain regional distribution of endocannabinoids: Implications for their biosynthesis and biological function. Biochem. Biophys. Res. Commun. 256:377-380.

Bornheim L.M., Kim K.Y., Chem B., Correia M.A. (1995) Microsomal cytochrome P-450-mediated liver and brain anandamide metabolism. Biochem. Pharmacology 50:667-686.

Bouaboula M., Poinot-Chazel C., Bourrié B., Canat X., Calandra B., Rinaldi-Carmona M., Le Fur G., Casellas P. (1995) Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem. J. 312:637-641.

Bouaboula M., Bourrie B., Rinaldi-Carmona M., Shire D., Le Fur G., Casellas P. (1995b) Stimulation of cannabinoid receptor CB1 induces Krox-24 expression in human astrocytoma cells. J. Biol. Chem. 270:13973-13980.

Bouaboula M., Poinot Chazel C., Marchand J., Canat X., Bourrie B., Rinaldi-Carmona M., Calandra B., Le Fur G., Casellas P. (1996) Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression. Eur. J. Biochem 237:704-711.

Bouaboula M., Perrachon S., Milligan L., Canat X., Rinaldi-Carmona M., Portier M., Barth F., Calandra B., Pecceu F., Lupker J., Maffrand J.P., Le Fur G., Casellas P. (1997) A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor. 1. Evidence for a new model of receptor/ligand interactions. J. Biol. Chem. 272:22330-22339.

Breivogel C.S., Sim C.J., Childers S.R. (1997) Regional differences in cannabinoid receptor/Gprotein coupling in rat brain. J. Pharmacol. Exp. Ther. 282:1632-1642.

Calandra B., Portier M., Kerneis A., Delpech M., Carillon C., Le Fur G., Ferrara P., Shire D. (1999) Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor. Eur. J. Pharmacol. 374:245-455.

Calignano A., LaRana G., Giuffrida A., Piomelli D. (1998) Control of pain iniciation by endogenous cannabinoids. Nature 394:277-281.

Chan P.K., Chan S.C., Yung W.H. (1998) Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist. Neuroreport 9:671-675.

Chen J., Paredes W., Li J., Smith D., Lowinson J., Gardner E.L. (1990) D9-Tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of concious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacol. 102:156-162.

Cravatt B.F., Giant D.K., Mayfield S.P., Boger D.L., Lerner R.A., Gigula N.B. (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature. 384:83-87.

Deadwyler S.A., Hampson R.E., Childers S.R. (1995) Functional significance of cannabinoid receptors in brain. pp 205-231. En Pertwee R. (ed) Cannabinoid receptors. Academic Press. London.

De Miguel R., Romero J., Muñoz R.M., García-Gil L., González S., Villanúa M.A., Makriyannis A., Ramos J.A., Fernández-Ruiz J.J. (1998) Effects of cannabinoids on prolactin and gonadotrophin secretion: involvement of changes in hypothalamic GABA inputs. Biochem. Pharmacol. 56:1331-1338.

Derkinren P., Toutant M., Burgaya F., Le Bert M., Siciliano J.C., De Franciscis V., Gelman M., Girault J.A. (1996) Regulation of a neural form of focal adhesion kinase by anandamide. Science 273:1719-1722.

Devane W.A., Dysarz F.A., Johnson M.R., Melvin L.S., Howlett A.C. (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 34:605-613.

Devane W.A., Hanus L., Breuer A., Pertwee R.G., Stevenson L.A., Griffin G., Gibson D., Mandelbaum A., Etinger A., Mechoulam R. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946-1949.

Di Marzo V., Fontana A., Cadas H., Schinelli S., Cimino G., Schwartz J.C., Piomelli D. (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686-691.

Facci L., Dal Toso R., Romanello S., Buriani A., Skaper S.D., Leon A. (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc. Natl. Acad. Sci. 92:3376-3380.

Fan P. (1995) Cannabinoid agonists inhibit the activation of 5HT3 receptors in rat nodose ganglion neurons. J. Neurophysiol 73:907-910.

Felder C., Glass M. (1998) Cannabinoid receptors and their endogenous agonists. Ann. Rev. Pharmacol and Toxicol. 38:179-200.

Fernández-Ruiz J.J., Muñoz R.M., Romero J., Villanúa M.A., Makriyannis A., Ramos J.A. (1997) Time-course of the effects of different cannabimimetics on prolactin and gonadotrophin secretion: evidence for the presence of CB1 receptors in hypothalamic structures and their involvement in the effects of cannabimimetics. Biochem. Pharmacol. 53:1919-1927.

Fernández-Ruiz J.J., Berrendero F., Hernández M.L., Romero J. Ramos J.A. (1999) Role of endocannabinoids in brain development. Life Sci. 65:725-736.

Fernández-Ruiz J.J., Berrendero F., Hernández M.L., Ramos J.A. (2000) The endogenous cannabinoid system and brain development. Trends Neurosci. 23:14-20.

French E.D., Dillon K., Wu X. (1997) Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8:649-652.

Gaoni Y., Mechoulam R. (1964) Isolation, structure, elucidation and partial synthesis of an active constituent of hashish”. J. Am. Chem. Soc. 86:1646-47.

García D.E., Brown S., Hille B., Mackie K. (1998) Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor. J. Neurosci. 18:2834-2841.

Gardner E.L., Paredes W., Smith D., Donner A., Milling C., Cohen D., Morrison D. (1988) Facilitation of brain stimulation reward by D9-tetrahydrocannabinol. Psychopharmacol. 96: 142-144.

Gardner E.L. (1992) Cannabinoid interaction with brain reward systems - The Neurobiological basis of cannabinoid abuse. pp. 275-335. En Marijuana/Cannabinoids. Neurobiology and Neurophysiology (eds. L. Murphy, A. Bartke), CRC Press, Boca Raton, FL.

Giuffrida A., Parsons L.H., Kerr T.M., Rodriguez F., Navarro M., Piomelli D. (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature Neuros. 2:358-363.

Gueudet C., Santucci V., Rinaldi-Carmona M., Soubrie P., Le Fur G. (1995) The CB1 cannabinoid receptor antagonist SR141716A affects A9 dopamine neuronal activity in the rats. Neuroreport 6:1421-1425.

Guzmán M., Fernández-Ruiz J.J., Sánchez C., Velasco G., Ramos J.A. (1995) Effects of anandamide on hepatic fatty acid metabolism. Biochem Pharmacol 50:885-888.

Guzmán M., Sánchez C. (1999) Effects of cannabinoids on energy metabolism. Life Sci. 65:657- 664.

Hampson R.E., Deadwyler S.A. (1999) Cannabinoids, hippocampal function and memory. Life Sci. 65:715-723 (1999).

Hansen H.S., Lauritzen L., Strand AM., Vinggaard AM., Frandsen A., Schousboe A. (1997) Characterization of glutamate-induced formation of Nacylphosphatidylethanolamine and N-acylethanolamine in cultured neocortical neurons. J. Neurochem. 69:753-61.

Hanus L., Gopher A., Almog S., Mechoulam R. (1993) Two new unsaturated fatty acids ethanolamides in brain that bind to the cannabinoid receptor. J. Med. Chem 36:3032-3034.

Herkenham M., Lynn A.B., Johnson M.R., Melvin L.S., De Costa B.R., Rice K.C. (1991a) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J. Neurosci. 11:563-583.

Herkenham M., Lynn A.B., de Costa B.R., Richfield E.K. (1991b) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat brain. Brain Res. 547:267-274.

Hernández M.L., García-Gil L., Berrendero F., Ramos J.A., Fernández-Ruiz J.J. (1997) D9- Tetrahydrocannabinol increases activity of tyrosine hydroxylase in cultured fetal mesencephalic neurons. J. Mol. Neurosci. 8:83-91.

Hernández M.L., Berrendero F., Suárez I., García-Gil L., Cebeira M., Mackie K., Ramos J.A., Fernández- Ruiz J.J. (1999) Cannabinoid CB1 receptors colocalize with tyrosine hydroxylase in cultured fetal mesencephalic neurons and their activation increases the levels of this enzyme. J. Neurochem. (en prensa).

Hillard C.J., Aucharmpach J.A. (1994) In vitro activation of brain protein kinase C by the cannabinoids. Biochem. Biophys. Acta 1120:163-170.

Hillard C.J., Edgemond W.S., Jarrahian A., Campbell W.A. (1997) Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilited diffusion. J. Neurochem 69:631-638.

Hoehe M.R., Caenazzo L., Martínez M.M., Hsieh W.T., Modi W.T., Gershon E.S., Bonner T.I. (1991) Genetic and physical mapping of the human cannabinoid receptor gene to chromosome 6 q14-q15. New Biol. 3:880-885.

Kaminski N.E. (1998) Regulation of the cAMP cascade, gene expression and inmune function by cannabinoid receptors. J. Neuroimmunol 83:124-132.

Kimura T., Ohta T., Watanabe K., Yoshimura H., Yamamoto I. (1998) Anandamide, an endogenous cannabinoid receptors ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor. Biol. Pharm. Bull. 21:224-226.

Kramer J., Ben-David M., (1987) Prolactin supression by (-)-D9-tetrahydrocannabinol (THC): involvement of serotoninergic and dopaminergic pathways. Endocrinology 103:452-458.

Lee M., Yang K.H., Kaminski N.E. (1995) Effects of putative cannabinoid receptor ligands, anandamide and 2-arachidonyl-glycerol, on immune function in B6C3F1 mouse splenocytes. J. Pharm. Exp. Ther. 275:529-536.

Levenes C., Daniel H., Soubrie P., Crepel F. (1998) Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells. J. Physiol. (London) 510:867-879.

Maccarrone M., van der Stelt M., Rossi A., Veldink G.A., Vliegenthart F.G., Finazzi A. (1998) Anandamide hydrolysis by human cells in culture and brain. J. Biol. Chem. 273:32332-32339.

Mackie K., Hille B. (1992) Cannabinoids inhibit Ntype calcium channels in neuroblastoma-glioma cells. Proc. Natl Acad. Sci. 89:3825-3829.

Mailleux P., Vanderhaeghen J.J. (1992) Distribution of neuronal cannabinoid receptors in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization hystochemistry. Neuroscience 48:655-668.

Mailleux P., Vanderhaeghem J.J. (1993) Glucocorticoid regulation of cannabinoid receptor Messenger RNA levels in rat caudate-putamen. An in situ hybridation study. Neurosci. Let. 156:51-53.

Mailleux P., Verslype M., Preud`Homme X., Vanderhaeghem J.J. (1994) Activation of multiple transcription factor genes by D9-tetrahydrocannabinol in rat forebrain. Neuroreport 5:1265-1268.

Maneuf Y.P., Crossman A.R., Brotchie J. (1996) Modulation of GABAergic transmission in the globus pallidus by the synthetic cannabinoid WIN 55,212-2. Synapse 22:382-385.

Maneuf Y.P., Brochie J.M. (1997) Paradoxical action of the cannabinoid WIN-55,212-2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices. Br. J. Pharmacol 120:1397-1398.

Manzanares J., Corchero J., Romero J., Fernández-Ruiz J.J., Ramos J.A., Fuentes J.A. (1999) Pharmacological and biochemical interactions between opioids and cannabinoids. Trends Pharmacol. Sci. 20:287-294.

Martin B.R., Mechoulam R., Razdan R.K. (1999) Discovery and characterization of endogenous cannabinoids. Life Sciences 65:573-595.

Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., Bonner T.I. (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561-564.

Mechoulam R., Hanus L., Martin B.R. (1994) Search for endogenous ligands of the cannabinoid receptors. Biochem. Pharmacol. 48:1537-1544.

Mechoulam R., Ben-Shabat S., Hanus L., Ligumsky M., Kaminski N.E., Schatz A.R., Gopher A., Almog S., Martin B.R., Compton D.R., Pertwee R.G., Griffin G., Bayewitch M., Barg J., Vogel Z. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptor. Biochem. Pharmacol. 50:83-90.

Molina-Holgado F., Amaro A., González M.I., Alvarez F.J., Leret M.L. (1996) Effects of maternal D9-tetrahydrocannabinol on developing serotonergic system. Eur. J. Pharmacol. 316:39-42.

Molina-Holgado F., Alvarez F., González M.I., Antonio M.T., Leret M.L. (1997) Maternal exposure to D9-tetrahydrocannabinol affects indolamine levels and turnover in adult male and female rat brain regions. Brain Res. Bull. 43:173-178.

Munro S., Thomas K.L., Abu-Shaar M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61-65.

Navarro M., Fernández-Ruiz J.J., de Miguel R., Hernández M.L., Cebeira M., Ramos J.A. (1993) An acute dose of D9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity. Behav. Brain Res. 57:37-46.

Pacheco M.A., Ward S.J., Childers S.R. (1993) Identification of cannabinoid receptors in cultures of rat cerebellar granule cells. Brain Res. 603:102-110.

Pérez-Reyes M., Bernstein S.H., White W.R., McDonald S.A., Hicks R.E. (1991) Antagonism of marihuana effects by indomethacin. Life Sci. 48:507-515.

Pertwee R.G. (1997) Pharmacoly of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther. 74:129-180.

Pertwee R.G. (1999) Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neural non-CB1 cannabinoid receptors. Life Sci. 65:597-605.

Reche I., Fuentes J.A., Ruiz-Gayo M. (1996) A role for central cannabinoid and opioid systems in peripheral D9-tetrahydrocannabinol-induced analgesia in mice. Eur. J. Pharmacol. 301:75-81.

Rhee M., Bayewitch M., Avidor-Reiss T., Levy R., Vogel Z. (1998) Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J. Neurochem 71:1525-1534.

Rinaldi-Carmona M., Barth F., Heaulme M., Shire D., Calandra B., Congy C., Martinez S., Marunai J., Neliat G., Caput D., Ferrara P., Soubrie J.C., Le Fur G. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett. 350:240-44.

Rinaldi-Carmona M., Barth F., Millan J., Derocq J.M., Casellas P., Congy C., Oustric D., Sarran M., Bouaboula M., Calandra B., Portier M., Shire D., Breliére J. C., Le Fur G. (1998) SR144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J. Pharmacol Exp. Ther. 284:644-650.

Rodriguez F., Gorriti M.A., Fernández-Ruiz J.J., Palomo T., Ramos J.A. (1994a) Down- regulation of rat brain cannabinoid binding sites after chronic D9-tetrahydrocannabinol treatment. Pharmacol. Biochem Behavior. 47:33-40.

Rodriguez F., Cebeira M., Ramos J.A., Martín M., Fernández-Ruiz J.J. (1994b) Cannabinoid receptor in rat brain areas: sexual differences, fluctuations during estrous cycle and changes after gonadectomy and sex steroid replacement. Life Science 54:159-170.

Romero J., García L., Ramos J.A., Fernández-Ruiz J.J. (1994) The putative cannabinoid receptor ligand, anandamide, stimulates hypothalamic tyrosine hydroxylase activity and inhibits prolactin release. Neuroend. Lett. 16:159-164.

Romero J., García L., Cebeira M., Zadrozny D., Fernández-Ruiz J.J., Ramos J.A. (1995a) The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behavior: role of nigrostriatal dopaminergic neurons. Life Sci. 56:2033-2040.

Romero J., de Miguel R., García-Palomero E., Fernández-Ruiz J.J., Ramos J.A. (1995b) Time-course of the effects of anandamide, the putative endogenous cannabinoid receptor ligand, on extrapyramidal function. Brain Res. 694:223-232.

Romero J., García L., Cebeira M., Fernández-Ruiz J.J., Ramos J.A. (1995c) Changes in rat brain cannabinoid binding sites after acute o chronic exposure to their endogenous agonist, anandamide or to D9-tetrahydrocannabinol. Pharmacol. Biochem Behavior 51:731-737.

Romero J., García-Palomero E., Lin S.Y., Ramos J.A., Makriyannis A., Fernández-Ruiz J.J. (1996a) Extrapyramidal effects of methanandamide, an analog of anandamide, the endogenous CB1 receptor ligand. Life Sci. 58:1249-1257.

Romero J., García-Palomero E., Fernández-Ruiz J.J., Ramos J.A. (1996b) Involvement of GABAB receptors in the motor inhibition produced by agonists of brain cannabinoid receptors Behavioral Pharmacology 7:299-302.

Romero J., García-Palomero E., Castro J.G., García-Gil L., Ramos J.A., Fernández-Ruiz J.J. (1997) Effects of chronic exposure to D9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Mol. Brain Res. 46:100-108.

Romero J., de Miguel R., Ramos J.A., Fernández-Ruiz J.J. (1998a) The activation of cannabinoid receptors in striatonigral GABAergic neurons inhibited GABA uptake. Life Sci. 62:351-363.

Romero J., Wenger T., de Miguel R., Ramos J.A., Fernández-Ruiz J.J. (1998b) Cannabinoid receptor binding did not vary in several hypothalamic nuclei after hypothalamic deafferentation. Life Sci. 63:351-356.

Romero J., Berrendero F., García L., de la Cruz P., Ramos J.A., Fernández-Ruiz J.J. (1998c) Loss of cannabinoid receptor binding and Messenger RNA levels and cannabinoid agonist-stimulated [35S]-guanylyl-5´-O-(thio)-triphosphate binding in the basal ganglia of aged rats. Neuroscience 84:1075-1083.

Sagan S., Venance L., Torrens Y., Cordier J., Glowinski J., Giaume C. (1999) Anandamide and WIN 55,212-2 inhibit cyclic AMP formation through G-protein-coupled receptors distinct from CB1 cannabinoid receptors in cultured astrocytes. Eur. J. Neurosci. 11:691-699.

Sánchez C., Galve-Roperh I., Rueda D., Guzmán M. (1998) Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the D9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. Mol Pharmacol. 54:834-843.

Schmid H.H.O., Schmid P.C., Natarajan V. (1990) Nacylated glycerophospholipid and their derivatives. Progr. Lipid Res. 29:1-43.

Shen M., Piser T.M., Seybold V.S., Thayer A. (1996) Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures. J. Neuros. 16:4322-4334 .

Shen M., Thayer S.A. (1998) Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol. Pharmacol. 54:459-462.

Shire D., Carillon C., Kaghad M., Calandra B., Rinaldi-Carmona M., Le Fur G., Caput D., Ferrara P. (1995). An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J. Biol Chem. 270:3726-3731.

Shivachar A.C., Martin B.R., Ellis E.F. (1996) Anandamide-and D9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1Hpyrazole-3-carboximide hydrochloride]. Biochem.Pharmacol. 51:669-676.

Skaper S.D., Buriani A., Dal Toso R., Petrelli L., Romanello S., Facci L., Leon A. (1996a) Palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc. Natl. Acad. Sci. 93:3984-3989.

Skaper S.D., Facci L., Romanello S., Leon A. (1996b) Mast cell activation causes delayed

neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway. J. Neurochem. 66:1157-1166.

Stefano G.B., Liu Y., Goligorsky M.S. (1996) Cannabinoid receptors are coupled to nitric oxide release in invertebrate immunocytes, microglia, and human monocytes. J. Biol. Chem. 271:19238-19242.

Stella N., Schweitzer P., Piomelli D. (1997) A second endogenous cannabinoid that modulates longterm potentiation. Nature 388:773-778.

Sugiura T., Kondo S., Sukagawa A., Nakane S., Shinoda A., Ittoh K., Yamashita A., Waku K. (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215:89-97.

Tersigni T.J., Rosenberg H.C. (1996) Local pressure application of cannabinoid agonists increases spontaneous activity of rat substantia nigra pars reticulata neurons without affecting response to iontophoretically-applied GABA. Brain Res. 733:184-192.

Thorat S.N., Bhargava H.N. (1994) Evidence for a bidirectional cross-tolerance between morphine and D9-tetrahydrocannabinol in mice. Eur. J. Pharmacol. 260:5-13.

Tsou K., Patrick S., Walker J.M. (1995) Physical withdrawal in rats tolerant to D9-tetrahidrocannabinol precipitated by a cannabinoid receptor antagonist. Eur. J. Pharmacol. 280:R13-R15.

Tsou K., Brown S., Sañudo-Peña M.C., Mackie K., Walker J.M. (1998a) Immunohistochemical distribution of cannabinoid-CB1 receptors in the rat central nervous system. Neuroscience 83:393-411.

Tsou K., Nogueron M.I., Muthian S., Sañudo-Peña M.C., Hillard C.J., Deutsch D.G., Walker J.M. (1998b) Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immunohistochemistry. Neurosci. Lett. 254:137-140.

Twichell W., Brown S., Mackie K. (1997) Cannabinoids inhibit N-and P/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol 78:43-50.

Valk P., Verbakel S., Vankan Y., Hol S., Mancham S., Ploemacher R., Mayen A., Lowenberg B., Delwel R. (1997) Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood 90:1448-1457.

Vela G., Ruiz-Gayo M., Fuentes J.A. (1995a) Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically treated with morphine. Neuropharmacol. 34:665-668.

Vela G., Fuentes J.A., Bonnin A., Fernández-Ruiz J.J., Ruiz-Gayo M. (1995b) Perinatal exposure to D9-tetrahydrocannabinol (D9-THC) leads to changes in opioid-related behavioral patterns in rats. Brain Res. 680:142-147.

Wakamatsu K., Masaki T., Itoh F., Kondo K., Sudo K. (1990) Isolation of fatty acid amide as an angiogenic principle from bovine mesentery. Biochem. Biophysic. Res. Commun 168:423-429.

Wartmann M., Campbell D., Subramaniam A., Burstein S.H., Davis R.J. (1995) The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide FEBS Letters. 359:133-136.

Westlake T.M., Howlett A.C., Bonner T.I., Matsuda L.A., Herkenham M. (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an “in vitro” receptor autoradiography and “in situ” hybridation histochemistry study of normal aged and Alzheimer`s brains. Neuroscience 63:637-652.

Wickens A.P., Pertwee R.G. (1993) D9-Tetrahydrocannabinol and anandamide enhance the ability of muscimol to induce catalepsy in the globus pallidus of rats. Eur. J. Pharmacol. 250:205-208.

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2000-06-15

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