{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:39:36Z","timestamp":1790663976780,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,5,13]]},"abstract":"\n Nifedipine, a drug used for treatment of hypertension and angina, exerts its effect by calcium channel blockade and nitric oxide production. We report here a previously uncharacterized action of nifedipine on central synaptic transmission that may partially explain its side effects. Nifedipine causes a long-lasting facilitation of tetrodotoxin-insensitive spontaneous glutamate release. This effect is independent of its L-type calcium channel blocking effect, and is not mimicked by other dihydropyridines such as nimodipine, nicardipine, or Bay K 8644. The effect was dose dependent, with EC\n 50<\/jats:sub>\n of 7.8 \u03bcM, with the lowest effective dose being 100 nM, a clinically relevant dose. At 10 \u03bcM, the increase is 14.7-fold. This effect is largely calcium-independent, because Cd\n 2+<\/jats:sup>\n , thapsigargin, or BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-\n N<\/jats:italic>\n ,\n N<\/jats:italic>\n ,\n N<\/jats:italic>\n \u2032,\n N<\/jats:italic>\n \u2032-tetraacetic acid-acetoxymethyl ester] did not inhibit the nifedipine effect. Thus, nifedipine seems to act on the release process downstream of calcium entry or release. Protein kinases A or C do not mediate its effect, because it is not blocked by inhibitors of these kinases. Our finding indicates that nifedipine may be a useful tool as a secretagogue to directly target the release process, but raises caution for its use as an L-type calcium channel blocker.\n <\/jats:p>","DOI":"10.1073\/pnas.0936131100","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T14:28:41Z","timestamp":1052836121000},"page":"6139-6144","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Nifedipine facilitates neurotransmitter release independently of calcium channels"],"prefix":"10.1073","volume":"100","author":[{"given":"Michiru","family":"Hirasawa","sequence":"first","affiliation":[{"name":"Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin J.","family":"Pittman","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,4,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1159\/000138382"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/4548"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061270"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.901"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.5.2542"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00378-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.5.3149"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-01-00046.1996"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(95)80005-S"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(91)90163-T"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018289"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(84)84233-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(98)00034-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/81781"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.015610"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.73.1.56"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(90)90040-F"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(87)90119-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00815.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199958030-00002"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.2000.00448.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-17-05312.1996"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90883-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-1-00461.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-06-01496.1991"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90076-4"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-22-08687.1997"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-01-00310.1994"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.2.571"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703873"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80603-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5421.1811"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00194-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-917"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00027.2001"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00001a017"},{"key":"e_1_3_3_37_2","first-page":"660","volume":"46","author":"Bangalore R","year":"1994","unstructured":"R Bangalore, N Baindur, A Rutledge, D J Triggle, R S Kass Mol Pharmacol 46, 660\u2013666 (1994).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/080370598438999"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002490050127"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1983.tb02720.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000013264.41234.24"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.9.865"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0936131100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:35:31Z","timestamp":1649788531000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0936131100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,24]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2003,5,13]]}},"alternative-id":["10.1073\/pnas.0936131100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0936131100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,24]]},"assertion":[{"value":"2002-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}