{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:44:57Z","timestamp":1762145097934,"version":"3.40.5"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI\/SAU-FCF\/57973\/2004"],"award-info":[{"award-number":["POCI\/SAU-FCF\/57973\/2004"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Adenosine A<jats:sub>1<\/jats:sub>and cannabinoid CB<jats:sub>1<\/jats:sub>receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A<jats:sub>1<\/jats:sub>and CB<jats:sub>1<\/jats:sub>receptors modulates cAMP accumulation in rat hippocampal slices. The CB<jats:sub>1<\/jats:sub>agonist WIN55212-2 (0.3\u201330\u2009<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>\u03bc<\/mml:mi><\/mml:mrow><\/mml:math>M) decreased forskolin-stimulated cAMP accumulation with an EC<jats:sub>50<\/jats:sub>of 6.6 \u00b1 2.7\u2009<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>\u03bc<\/mml:mi><\/mml:mrow><\/mml:math>M and an<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:msub><mml:mrow><mml:mi>E<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi>max<\/mml:mi><mml:mo>\u2061<\/mml:mo><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>of 31% \u00b1 2%, whereas for the A<jats:sub>1<\/jats:sub>agonist, N<jats:sup>6<\/jats:sup>-cyclopentyladenosine (CPA, 10\u2013150\u2009nM), an EC<jats:sub>50<\/jats:sub>of 35 \u00b1 19\u2009nM, and an<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:msub><mml:mrow><mml:mi>E<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi>max<\/mml:mi><mml:mo>\u2061<\/mml:mo><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>of 29% \u00b1 5 were obtained. The combined inhibitory effect of WIN55212-2 (30\u2009<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mrow><mml:mi>\u03bc<\/mml:mi><\/mml:mrow><\/mml:math>M) and CPA (100\u2009nM) on cAMP accumulation was 41% \u00b1 6% (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>4<\/mml:mn><\/mml:math>), which did not differ (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>P<\/mml:mi><mml:mo>&gt;<\/mml:mo><mml:mn>0.7<\/mml:mn><\/mml:math>) from the sum of the individual effects of each agonist (43% \u00b1 8%) but was different (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>) from the effects of CPA or WIN55212-2 alone. Preincubation with CPA (100\u2009nM) for 95\u2009min caused desensitization of adenosine A<jats:sub>1<\/jats:sub>activity, which did not modify the effect of WIN55212-2 (30\u2009<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\"><mml:mrow><mml:mi>\u03bc<\/mml:mi><\/mml:mrow><\/mml:math>M) on cAMP accumulation. In conclusion, the combined effect of CB<jats:sub>1<\/jats:sub>and A<jats:sub>1<\/jats:sub>receptors on cAMP formation is additive and CB<jats:sub>1<\/jats:sub>receptor activity is not affected by short-term A<jats:sub>1<\/jats:sub>receptor desensitization.<\/jats:p>","DOI":"10.1155\/2015\/872684","type":"journal-article","created":{"date-parts":[[2015,1,18]],"date-time":"2015-01-18T21:00:30Z","timestamp":1421614830000},"page":"1-9","source":"Crossref","is-referenced-by-count":9,"title":["The Combined Inhibitory Effect of the Adenosine A<sub>1<\/sub>and Cannabinoid CB<sub>1<\/sub>Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A<sub>1<\/sub>Receptor Desensitization"],"prefix":"10.1155","volume":"2015","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9529-8342","authenticated-orcid":true,"given":"Andr\u00e9","family":"Serpa","sequence":"first","affiliation":[{"name":"Health Sciences Research Center, University of Beira Interior (CICS-UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Sara","family":"Correia","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center, University of Beira Interior (CICS-UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Joaquim A.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal"},{"name":"Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal"}]},{"given":"Ana M.","family":"Sebasti\u00e3o","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal"},{"name":"Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal"}]},{"given":"Jos\u00e9 F.","family":"Cascalheira","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center, University of Beira Interior (CICS-UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas D\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2005"},{"issue":"6","key":"2","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1523\/JNEUROSCI.17-06-01993.1997","volume":"17","year":"1997","journal-title":"The Journal of Neuroscience"},{"issue":"13","key":"3","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/j.1460-2075.1995.tb07306.x","volume":"14","year":"1995","journal-title":"The EMBO 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