{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:47:04Z","timestamp":1792716424931,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2285,"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":[[2002,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Nitric oxide (NO) is a key modulator of cellular Ca<jats:sup>2+<\/jats:sup> signalling and a determinant of mitochondrial function. Here, we demonstrate that NO governs capacitative Ca<jats:sup>2+<\/jats:sup> entry (CCE) into HEK293 cells by impairment of mitochondrial Ca<jats:sup>2+<\/jats:sup> handling.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Authentic NO as well as the NO donors 1\u2010[2\u2010(carboxylato)pyrrolidin\u20101\u2010yl]diazem\u20101\u2010ium\u20101,2\u2010diolate (ProliNO) and 2\u2010(N,N\u2010diethylamino)\u2010diazenolate\u20102\u2010oxide (DEANO) suppressed CCE activated by thapsigargin (TG)\u2010induced store depletion. Threshold concentrations for inhibition of CCE by ProliNO and DEANO were 0.3 and 1 \u03bc<jats:sc>M<\/jats:sc>, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NO\u2010induced inhibition of CCE was not mimicked by peroxynitrite (100 \u03bc<jats:sc>M<\/jats:sc>), the peroxynitrite donor 3\u2010morpholino\u2010sydnonimine (SIN\u20101, 100 \u03bc<jats:sc>M<\/jats:sc>) or 8\u2010bromoguanosine 3\u2032,5\u2032\u2010cyclic monophosphate (8\u2010BrcGMP, 1 m<jats:sc>M<\/jats:sc>). In addition, the guanylyl cyclase inhibitor 1H\u2010[1,2,4] oxadiazole[4,3\u2010a] quinoxalin\u20101\u2010one (ODQ, 30 \u03bc<jats:sc>M<\/jats:sc>) failed to antagonize the inhibitory action of NO on CCE.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>DEANO (1\u201310 \u03bc<jats:sc>M<\/jats:sc>) suppressed mitochondrial respiration as evident from inhibition of cellular oxygen consumption. Experiments using fluorescent dyes to monitor mitochondrial membrane potential and mitochondrial Ca<jats:sup>2+<\/jats:sup> levels, respectively, indicated that DEANO (10 \u03bc<jats:sc>M<\/jats:sc>) depolarized mitochondria and suppressed mitochondrial Ca<jats:sup>2+<\/jats:sup> sequestration. The inhibitory effect of DEANO on Ca<jats:sup>2+<\/jats:sup> uptake into mitochondria was confirmed by recording mitochondrial Ca<jats:sup>2+<\/jats:sup> during agonist stimulation in HEK293 cells expressing ratiometric\u2010pericam in mitochondria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>DEANO (10 \u03bc<jats:sc>M<\/jats:sc>) failed to inhibit Ba<jats:sup>2+<\/jats:sup> entry into TG\u2010stimulated cells when extracellular Ca<jats:sup>2+<\/jats:sup> was buffered below 1 \u03bc<jats:sc>M<\/jats:sc>, while clear inhibition of Ba<jats:sup>2+<\/jats:sup> entry into store depleted cells was observed when extracellular Ca<jats:sup>2+<\/jats:sup> levels were above 10 \u03bc<jats:sc>M<\/jats:sc>. Moreover, buffering of intracellular Ca<jats:sup>2+<\/jats:sup> by use of N,N\u2032\u2010[1,2\u2010ethanediylbis(oxy\u20102,1\u2010phenylene)] bis [N\u2010[25\u2010[(acetyloxy) methoxy]\u20102\u2010oxoethyl]]\u2010, bis[(acetyloxy)methyl] ester (BAPTA\/AM) eliminated inhibition of CCE by NO, indicating that the observed inhibitory effects are based on an intracellular, Ca<jats:sup>2+<\/jats:sup> dependent\u2010regulatory process.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data demonstrate that NO effectively inhibits CCE cells by cGMP\u2010independent suppression of mitochondrial function. We suggest disruption of local Ca<jats:sup>2+<\/jats:sup> handling by mitochondria as a key mechanism of NO induced suppression of CCE.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>137<\/jats:bold>, 821\u2013830. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704949\">10.1038\/sj.bjp.0704949<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704949","type":"journal-article","created":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T05:21:57Z","timestamp":1036128117000},"page":"821-830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Nitric oxide inhibits capacitative Ca<sup>2+<\/sup> entry by suppression of mitochondrial Ca<sup>2+<\/sup> handling"],"prefix":"10.1111","volume":"137","author":[{"given":"Baskaran","family":"Thyagarajan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Malli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang F","family":"Graier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Groschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(95)90071-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(99)00025-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00375-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(97)01087-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.2.210"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(96)00078-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36843-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000016321"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.017053"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.109bx.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_7_13_1","first-page":"G350","article-title":"Nitric oxide production regulates cGMP formation and calcium influx in pancreatic acinar cells","volume":"266","author":"GUKOVSKAYA A.","year":"1994","journal-title":"Am. 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