{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:23:59Z","timestamp":1759335839819},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3650,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Previous studies have shown that GABA<jats:sub>B<\/jats:sub> receptors facilitate cyclic AMP formation in brain slices likely through an indirect mechanism involving intracellular second messengers. In the present study, we have investigated whether a positive coupling of GABA<jats:sub>B<\/jats:sub> receptors to adenylyl cyclase could be detected in a cell\u2010free preparation of rat olfactory bulb, a brain region where other G<jats:sub>i<\/jats:sub>\/G<jats:sub>o<\/jats:sub>\u2010coupled neurotransmitter receptors have been found to stimulate the cyclase activity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The GABA<jats:sub>B<\/jats:sub> receptor agonist (\u2212)\u2010baclofen significantly increased basal adenylyl cyclase activity in membranes of the granule cell and external plexiform layers, but not in the olfactory nerve\u2010glomerular layer. The adenylyl cyclase stimulation was therefore examined in granule cell layer membranes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The (\u2212)\u2010baclofen stimulation (pD<jats:sub>2<\/jats:sub>=4.53) was mimicked by 3\u2010aminopropylphosphinic acid (pD<jats:sub>2<\/jats:sub>=4.60) and GABA (pD<jats:sub>2<\/jats:sub>=3.56), but not by (+)\u2010baclofen, 3\u2010aminopropylphosphonic acid, muscimol and isoguvacine. The stimulatory effect was counteracted by the GABA<jats:sub>B<\/jats:sub> receptor antagonists CGP 35348 (pA<jats:sub>2<\/jats:sub>=4.31), CGP 55845 A (pA<jats:sub>2<\/jats:sub>=7.0) and 2\u2010hydroxysaclofen (pK<jats:sub>i<\/jats:sub>=4.22). Phaclofen (1\u2003m<jats:sc>M<\/jats:sc>) was inactive.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The (\u2212)\u2010baclofen stimulation was not affected by quinacrine, indomethacin, nordihydroguaiaretic acid and staurosporine, but was completely prevented by pertussis toxin and significantly reduced by the \u03b1 subunit of transducin, a \u03b2\u03b3 scavenger. The \u03b2\u03b3 subunits of transducin stimulated the cyclase activity and this effect was not additive with that produced by (\u2212)\u2010baclofen.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the external plexiform and granule cell layers, but not in the olfactory nerve\u2010glomerular layer, (\u2212)\u2010baclofen enhanced the adenylyl cyclase stimulation elicited by the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) 38.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Conversely, the adenylyl cyclase activity stimulated by either forskolin or Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010(Ca<jats:sup>2+<\/jats:sup>\/CaM) was inhibited by (\u2212)\u2010baclofen in all the olfactory bulb layers examined.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data demonstrate that in specific layers of rat olfactory bulb activation of GABA<jats:sub>B<\/jats:sub> receptors enhances basal and neurotransmitter\u2010stimulated adenylyl cyclase activities by a mechanism involving \u03b2\u03b3 subunits of G<jats:sub>i<\/jats:sub>\/G<jats:sub>o<\/jats:sub>. This positive coupling is associated with a widespread inhibitory effect on forskolin\u2010 and Ca<jats:sup>2+<\/jats:sup>\/CaM\u2010stimulated cyclic AMP formation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 657\u2013664; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702349\">10.1038\/sj.bjp.0702349<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702349","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:41:09Z","timestamp":1106941269000},"page":"657-664","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["GABA<sub>B<\/sub> receptor\u2010mediated stimulation of adenylyl cyclase activity in membranes of rat olfactory bulb"],"prefix":"10.1111","volume":"126","author":[{"given":"Maria C","family":"Olianas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Onali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90056-P"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.33.040193.000545"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90098-4"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(90)90144-S"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00120-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1986.tb00682.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(84)90264-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(87)90028-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/356159a0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.10173"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/361536a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(84)90268-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12591.x"},{"key":"e_1_2_7_17_1","first-page":"53","article-title":"Characterization of the relationship between \u03b3\u2010aminobutyric acid B agonists and transmitter\u2010coupled cyclic nucleotide\u2010generating systems in rat brain","volume":"27","author":"KARBON E.W.","year":"1985","journal-title":"Mol. 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