{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:15:22Z","timestamp":1792224922323,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":188,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:p>Rhythmic noradrenergic signaling from the hypothalamic clock in the suprachiasmatic nucleus to the pineal gland causes an increase in intracellular cAMP which regulates the circadian fluctuation of melatonin synthesis. The activation of phospholipase C (PLC)\u2010coupled P2Y<jats:sub>2<\/jats:sub> receptors upon treatment with ATP and UTP exclusively inhibited the isoproterenol\u2010stimulated cAMP production in mouse pineal gland tumor cells. However, the activation of other PLC\u2010coupled receptors including P2Y<jats:sub>1<\/jats:sub> and bombesin receptors had little or no effect on the isoproterenol\u2010stimulated cAMP production. Also, ATP did not inhibit cAMP production caused by forskolin, prostaglandin E<jats:sub>2<\/jats:sub>, or the adenosine analog NECA. These results suggest a selective coupling between signalings of P2Y<jats:sub>2<\/jats:sub> and \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic receptors. The binding of [<jats:sup>3<\/jats:sup>H]CGP12177 to \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic receptors was not effected by the presence of ATP or UTP. Ionomycin decreased the isoproterenol\u2010stimulated cAMP production, whereas phorbol 12\u2010myristate 13\u2010acetate slightly potentiated the isoproterenol response. Chelation of intracellular Ca<jats:sup>2+<\/jats:sup>, however, had little effect on the ATP\u2010induced inhibition of cAMP production, while it completely reversed the ionomycin\u2010induced inhibition. Treatment of cells with pertussis toxin almost completely blocked the inhibitory effect of nucleotides. Pertussis toxin also inhibited the nucleotide\u2010induced increase in intracellular Ca<jats:sup>2+<\/jats:sup> and inositol 1,4,5\u2010trisphosphate production by 30\u201340%, suggesting that the ATP\u2010mediated inhibition of the cAMP generation and the partial activation of PLC are mediated by pertussis toxin\u2010sensitive G<jats:sub>i<\/jats:sub>\u2010protein. We conclude that one of the functions of P2Y<jats:sub>2<\/jats:sub> receptors on the pineal gland is the selective inhibition of \u03b2\u2010adrenergic receptor\u2010mediated signaling pathways via the inhibitory G\u2010proteins.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2001.00367.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:55:21Z","timestamp":1047452121000},"page":"1475-1485","source":"Crossref","is-referenced-by-count":16,"title":["Selective inhibition of \u03b2<sub>2<\/sub>\u2010adrenergic receptor\u2010mediated cAMP generation by activation of the P2Y<sub>2<\/sub> receptor in mouse pineal gland tumor cells"],"prefix":"10.1111","volume":"77","author":[{"given":"Byung\u2010Chang","family":"Suh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010So","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uk","family":"Namgung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong\u2010Tai","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,20]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"84","article-title":"Comparison of P2 purinergic receptors of aortic endothelial cells with those of adrenal medulla: evidence for heterogeneity of receptor subtype and of inositol phosphate response","volume":"38","author":"Allsup D. J.","year":"1990","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(93)90015-R"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-6147(00)89001-x"},{"key":"e_1_2_7_5_1","first-page":"1140","article-title":"Identification of a P2Y\u2010purinergic receptor that inhibits adenylyl cyclase","volume":"267","author":"Boyer J. L.","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199701163360306"},{"key":"e_1_2_7_7_1","first-page":"605","article-title":"Control of pineal N\u2010acetylserotonin by a \u03b2\u2010adrenergic receptor","volume":"9","author":"Brownstein M.","year":"1973","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2650421"},{"key":"e_1_2_7_9_1","first-page":"532","article-title":"A reagent for the single\u2010step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski P.","year":"1993","journal-title":"Biotechniques"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1978.235.3.C97"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2560959"},{"key":"e_1_2_7_12_1","first-page":"39","volume-title":"Melatonin Biosynthesis, Physiological Effects and Clinical Applications","author":"Ebadi M.","year":"1993"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb13037.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of\u00a0Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz G.","year":"1985","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90537-L"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(82)90175-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90848-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"11830","DOI":"10.1016\/S0021-9258(17)32648-0","article-title":"Identification of a uridine nucleotide\u2010selective G protein\u2010linked receptor that activates phospholipase C","volume":"269","author":"Lazarowski E. R.","year":"1994","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15175.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(97)00022-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021930"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"12960","DOI":"10.1016\/S0021-9258(19)38253-5","article-title":"Molecular cloning and expression of the \u03b21\u2010adrenergic receptor gene","volume":"265","author":"Machida C. A.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7135"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-2999(00)00416-7"},{"key":"e_1_2_7_25_1","first-page":"1185","article-title":"P2U\u2010purinergic receptors on C6\u20132B rat glioma cells: modulation of cytosolic Ca2+ and cAMP levels by protein kinase C","volume":"44","author":"Munshi R.","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_26_1","first-page":"224","article-title":"Uridine nucleotide selectivity of three phospholipase C\u2010activating P2 receptors: identification of a UDP\u2010selective, a UTP\u2010selective, and an ATP\u2010 and UTP\u2010specific receptor","volume":"50","author":"Nicholas R. A.","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1997.tb00350.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-4-2150"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304-3940(97)00684-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"13483","DOI":"10.1016\/S0021-9258(19)76452-7","article-title":"P2\u2010purinergic receptors are coupled to two signal transduction systems leading\u00a0to\u00a0inhibition of cAMP generation and to production of inositol trisphosphate in rat hepatocytes","volume":"262","author":"Okajima F.","year":"1987","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_31_1","first-page":"413","article-title":"Receptors for purines and pyrimidines","volume":"50","author":"Ralevic V.","year":"1998","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-12-2-151"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5463.154"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(99)01199-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90069-8"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67010287.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/314359a0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64062500.x"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.51.32753"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68041622.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702248"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0740169.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.4.2319"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3881822"},{"key":"e_1_2_7_45_1","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1523\/JNEUROSCI.18-06-02056.1998","article-title":"Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes","volume":"18","author":"Yamada H.","year":"1998","journal-title":"J. Neurosci."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03306.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90016-7"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1471-4159.2001.00367.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1471-4159.2001.00367.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T10:41:46Z","timestamp":1697625706000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1471-4159.2001.00367.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6,15]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,6,15]]}},"alternative-id":["10.1046\/j.1471-4159.2001.00367.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1471-4159.2001.00367.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6,15]]}}}