;PMID: 8760035 ;source_file_1732.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..43] = [t:0..43] ;1)sentence:[e:49..160] = [t:49..160] ;2)section:[e:164..189] = [t:164..189] ;3)section:[e:193..267] = [t:193..267] ;4)sentence:[e:271..476] = [t:271..476] ;5)sentence:[e:477..638] = [t:477..638] ;6)sentence:[e:639..804] = [t:639..804] ;7)sentence:[e:805..1088] = [t:805..1088] ;8)sentence:[e:1089..1276] = [t:1089..1276] ;9)sentence:[e:1277..1503] = [t:1277..1503] ;10)sentence:[e:1504..1603] = [t:1504..1603] ;11)sentence:[e:1605..1955] = [t:1605..1955] ;12)sentence:[e:1956..2216] = [t:1956..2216] ;13)sentence:[e:2217..2440] = [t:2217..2440] ;14)section:[e:2444..2488] = [t:2444..2488] ;section 0 Span:0..43 ;Am J Physiol. 1996 Jul;271(1 Pt 1):C103-11. (SEC (FRAG (NNP:[0..2] Am) (NNP:[3..4] J) (NNP:[5..12] Physiol) (.:[12..13] .) (CD:[14..18] 1996) (.:[19..26] Jul;271) (-LRB-:[26..27] -LRB-) (CD:[27..28] 1) (NN:[29..31] Pt) (CD:[32..33] 1) (-RRB-:[33..34] -RRB-) (CD:[34..39] :C103) (::[39..40] -) (CD:[40..42] 11) (.:[42..43] .))) ;sentence 1 Span:49..160 ;Cytochrome P-450 metabolites mediate extracellular Ca(2+)-induced inhibition ;of apical K+ channels in the TAL. ;[49..65]:cyp450:"Cytochrome P-450" ;[66..77]:substance:"metabolites" ;[100..106]:substance:"Ca(2+)" ;[137..139]:substance:"K+" (SENT (S-HLN (NP-SBJ (NML (NN:[49..59] Cytochrome) (NN:[60..65] P-450)) (NNS:[66..77] metabolites)) (VP (VBP:[78..85] mediate) (NP (NP (JJ:[86..99] extracellular) (ADJP (NN:[100..106] Ca-LRB-2+-RRB-) (HYPH:[106..107] -) (VBN:[107..114] induced)) (NN:[115..125] inhibition)) (PP (IN:[126..128] of) (NP (JJ:[130..136] apical) (NN:[137..139] K+) (NNS:[140..148] channels)))) (PP-LOC (IN:[149..151] in) (NP (DT:[152..155] the) (NN:[156..159] TAL)))) (.:[159..160] .))) ;section 2 Span:164..189 ;Wang WH, Lu M, Hebert SC. (SEC (FRAG (NNP:[164..168] Wang) (NNP:[169..171] WH) (,:[171..172] ,) (NNP:[173..175] Lu) (NNP:[176..178] M,) (NNP:[179..185] Hebert) (NNP:[186..188] SC) (.:[188..189] .))) ;section 3 Span:193..267 ;Department of Pharmacology, New York Medical College, Valhalla 10595, USA. (SEC (FRAG (NNP:[193..203] Department) (IN:[204..206] of) (NNP:[207..219] Pharmacology) (,:[219..220] ,) (NNP:[221..224] New) (NNP:[225..229] York) (NNP:[230..237] Medical) (NNP:[238..245] College) (,:[245..246] ,) (NNP:[247..255] Valhalla) (CD:[256..261] 10595) (,:[261..262] ,) (NNP:[263..266] USA) (.:[266..267] .))) ;sentence 4 Span:271..476 ;We used the patch-clamp technique to study the effect of extracellular Ca2+ ;(Ca2+o) on the activity of the apical 70-pS K+ channel in the isolated ;split-open thick ascending limb (TAL) of the rat kidney. ;[342..346]:substance:"Ca2+" ;[349..354]:substance:"Ca2+o" ;[392..394]:substance:"K+" (SENT (S (NP-SBJ (PRP:[271..273] We)) (VP (VBD:[274..278] used) (NP (DT:[279..282] the) (NML (NN:[283..288] patch) (HYPH:[288..289] -) (NN:[289..294] clamp)) (NN:[295..304] technique)) (S-PRP (NP-SBJ (-NONE-:[304..304] *)) (VP (TO:[305..307] to) (NP (VB:[308..313] study) (NP (NP (DT:[314..317] the) (NN:[318..324] effect)) (PP (IN:[325..327] of) (NP (NP (JJ:[328..341] extracellular) (NN:[342..346] Ca2+)) (NP (-LRB-:[348..349] -LRB-) (NN:[349..354] Ca2+o) (-RRB-:[354..355] -RRB-)))) (PP (IN:[356..358] on) (NP (NP (DT:[359..362] the) (NN:[363..371] activity)) (PP (IN:[372..374] of) (NP (DT:[375..378] the) (JJ:[379..385] apical) (NML (CD:[386..388] 70) (HYPH:[388..389] -) (NN:[389..391] pS)) (NN:[392..394] K+) (NN:[395..402] channel)))))) (PP-LOC (IN:[403..405] in) (NP (NP (NP (DT:[406..409] the) (VBN:[410..418] isolated) (ADJP (VBN:[420..425] split) (HYPH:[425..426] -) (JJ:[426..430] open)) (JJ:[431..436] thick) (VBG:[437..446] ascending) (NN:[447..451] limb)) (NP (-LRB-:[452..453] -LRB-) (NN:[453..456] TAL) (-RRB-:[456..457] -RRB-))) (PP (IN:[458..460] of) (NP (DT:[461..464] the) (NN:[465..468] rat) (NN:[469..475] kidney))))))))) (.:[475..476] .))) ;sentence 5 Span:477..638 ;Raising Ca2+o from 1.1 to 5 mM reversibly reduced the activity of the 70-pS ;K+ channel in cell-attached patches to 16 +/- 2% of the control value within ;300 s. ;[485..490]:substance:"Ca2+o" ;[496..499]:quantitative-value:"1.1" ;[504..505]:quantitative-value:"5" ;[506..508]:quantitative-units:"mM" ;[554..556]:substance:"K+" ;[594..603]:quantitative-value:"16 +/- 2%" ;[632..635]:quantitative-value:"300" ;[636..637]:quantitative-units:"s" (SENT (S (S-NOM-SBJ (NP-SBJ (-NONE-:[477..477] *)) (VP (VBG:[477..484] Raising) (NP (NP (NN:[485..490] Ca2+o)) (PP (IN:[491..495] from) (NP (CD:[496..499] 1.1) (NML-1 (-NONE-:[499..499] *RNR*)))) (PP (TO:[501..503] to) (NP (CD:[504..505] 5) (NML-1 (-NONE-:[505..505] *RNR*)))) (NML-1 (NN:[506..508] mM))))) (ADVP (RB:[509..519] reversibly)) (VP (VBD:[520..527] reduced) (NP (NP (DT:[528..531] the) (NN:[532..540] activity)) (PP (IN:[541..543] of) (NP (DT:[544..547] the) (NML (CD:[548..550] 70) (HYPH:[550..551] -) (NN:[551..553] pS)) (NN:[554..556] K+) (NN:[557..564] channel)))) (PP-LOC (IN:[565..567] in) (NP (ADJP (NN:[568..572] cell) (HYPH:[572..573] -) (VBN:[573..581] attached)) (NNS:[583..590] patches))) (PP (TO:[591..593] to) (NP (NP (QP (CD:[594..596] 16) (SYM:[597..600] +/-) (CD:[601..602] 2)) (NN:[602..603] %)) (PP (IN:[604..606] of) (NP (NP (DT:[607..610] the) (NN:[611..618] control) (NN:[619..624] value)) (PP (IN:[625..631] within) (NP (CD:[632..635] 300) (NN:[636..637] s)))))))) (.:[637..638] .))) ;sentence 6 Span:639..804 ;In addition, 50 microM neomycin mimicked the effect of an increase in Ca2+o ;on channel activity in cell-attached patches and completely inhibited ;channel activity. ;[652..654]:quantitative-value:"50" ;[655..661]:quantitative-units:"microM" ;[663..671]:substance:"neomycin" ;[710..715]:substance:"Ca2+o" (SENT (S (PP (IN:[639..641] In) (NP (NN:[642..650] addition))) (,:[650..651] ,) (NP-SBJ (NML (CD:[652..654] 50) (NN:[655..661] microM)) (NN:[663..671] neomycin)) (VP (VP (VBD:[672..680] mimicked) (NP (NP (DT:[681..684] the) (NN:[685..691] effect)) (PP (IN:[692..694] of) (NP (NP (DT:[695..697] an) (NN:[698..706] increase)) (PP (IN:[707..709] in) (NP (NN:[710..715] Ca2+o))))) (PP (IN:[716..718] on) (NP (NP (NN:[719..726] channel) (NN:[727..735] activity)) (PP-LOC (IN:[736..738] in) (NP (ADJP (NN:[740..744] cell) (HYPH:[744..745] -) (VBN:[745..753] attached)) (NNS:[754..761] patches))))))) (CC:[762..765] and) (VP (ADVP (RB:[766..776] completely)) (VBD:[777..786] inhibited) (NP (NN:[787..794] channel) (NN:[795..803] activity)))) (.:[803..804] .))) ;sentence 7 Span:805..1088 ;The effect of neomycin on the channel activity in cell-attached patches is ;an indirect effect, since addition of 50 microM neomycin on the 70-pS K+ ;channel in inside-out patches reduced only the apparent amplitude of the ;channel current without changing channel open probability. ;[820..828]:substance:"neomycin" ;[920..922]:quantitative-value:"50" ;[923..929]:quantitative-units:"microM" ;[930..938]:substance:"neomycin" ;[952..954]:substance:"K+" (SENT (S (NP-SBJ (NP (DT:[805..808] The) (NN:[809..815] effect)) (PP (IN:[816..818] of) (NP (NN:[820..828] neomycin))) (PP (IN:[829..831] on) (NP (DT:[832..835] the) (NN:[836..843] channel) (NN:[844..852] activity))) (PP-LOC (IN:[853..855] in) (NP (ADJP (NN:[856..860] cell) (HYPH:[860..861] -) (VBN:[861..869] attached)) (NNS:[870..877] patches)))) (VP (VBZ:[878..880] is) (NP-PRD (DT:[881..883] an) (JJ:[884..892] indirect) (NN:[893..899] effect)) (,:[899..900] ,) (SBAR-ADV (IN:[902..907] since) (S (NP-SBJ (NP (NN:[908..916] addition)) (PP (IN:[917..919] of) (NP (NML (CD:[920..922] 50) (NN:[923..929] microM)) (NN:[930..938] neomycin))) (PP (IN:[939..941] on) (NP (DT:[942..945] the) (NML (CD:[946..948] 70) (HYPH:[948..949] -) (NN:[949..951] pS)) (NN:[952..954] K+) (NN:[955..962] channel))) (PP-LOC (IN:[963..965] in) (ADJP (NN:[966..972] inside) (HYPH:[972..973] -) (RP:[973..976] out)) (NNS:[978..985] patches))) (VP (VBD:[986..993] reduced) (NP (NP (ADVP (RB:[994..998] only)) (DT:[999..1002] the) (JJ:[1003..1011] apparent) (NN:[1012..1021] amplitude)) (PP (IN:[1022..1024] of) (NP (DT:[1025..1028] the) (NN:[1029..1036] channel) (NN:[1037..1044] current)))) (PP (IN:[1045..1052] without) (S-NOM (NP-SBJ (-NONE-:[1052..1052] *)) (VP (VBG:[1054..1062] changing) (NP (NML (NN:[1063..1070] channel) (JJ:[1071..1075] open)) (NN:[1076..1087] probability))))))))) (.:[1087..1088] .))) ;sentence 8 Span:1089..1276 ;We examined further the role of protein kinase C (PKC) and the cytochrome ;P-450-dependent metabolites of arachidonic acid in mediating the Ca2+o ;-induced inhibition of channel activity. ;[1121..1138]:substance:"protein kinase C" ;[1140..1143]:substance:"PKC" ;[1153..1169]:cyp450:"cytochrome P-450" ;[1180..1191]:substance:"metabolites" ;[1195..1212]:substance:"arachidonic acid" ;[1230..1235]:substance:"Ca2+o" (SENT (S (NP-SBJ (PRP:[1089..1091] We)) (VP (VBD:[1092..1100] examined) (ADVP-EXT (RBR:[1101..1108] further)) (NP (NP (DT:[1109..1112] the) (NN:[1113..1117] role)) (PP (IN:[1118..1120] of) (NP (NP (NP (NN:[1121..1128] protein) (NN:[1130..1136] kinase) (NN:[1137..1138] C)) (NP (-LRB-:[1139..1140] -LRB-) (NN:[1140..1143] PKC) (-RRB-:[1143..1144] -RRB-))) (CC:[1145..1148] and) (NP (NP (DT:[1149..1152] the) (ADJP (NML (NN:[1153..1163] cytochrome) (NN:[1164..1169] P-450)) (HYPH:[1169..1170] -) (JJ:[1170..1179] dependent)) (NNS:[1180..1191] metabolites)) (PP (IN:[1192..1194] of) (NP (JJ:[1195..1206] arachidonic) (NN:[1208..1212] acid)))))) (PP (IN:[1213..1215] in) (S-NOM (NP-SBJ (-NONE-:[1215..1215] *)) (VP (VBG:[1216..1225] mediating) (NP (NP (DT:[1226..1229] the) (ADJP (NN:[1230..1235] Ca2+o) (HYPH:[1236..1237] -) (VBN:[1237..1244] induced)) (NN:[1245..1255] inhibition)) (PP (IN:[1256..1258] of) (NP (NN:[1259..1266] channel) (NN:[1267..1275] activity))))))))) (.:[1275..1276] .))) ;sentence 9 Span:1277..1503 ;Addition of phorbol 12-myristate 13-acetate (2 microM) reversibly blocked ;channel activity in cell-attached patches to 4 +/- 1% of the control value, ;whereas 75 nM calphostin C increased the channel activity by 115 +/- 10%. ;[1290..1321]:substance:"phorbol 12-myristate 13-acetate" ;[1323..1324]:quantitative-value:"2" ;[1325..1331]:quantitative-units:"microM" ;[1398..1406]:quantitative-value:"4 +/- 1%" ;[1437..1439]:quantitative-value:"75" ;[1440..1442]:quantitative-units:"nM" ;[1444..1456]:substance:"calphostin C" ;[1491..1502]:quantitative-value:"115 +/- 10%" (SENT (S (NP-SBJ (NP (NN:[1277..1285] Addition)) (PP (IN:[1286..1288] of) (NP (NN:[1290..1297] phorbol) (NN:[1298..1310] 12-myristate) (NN:[1311..1321] 13-acetate) (PRN (-LRB-:[1322..1323] -LRB-) (NP (CD:[1323..1324] 2) (NN:[1325..1331] microM)) (-RRB-:[1331..1332] -RRB-))))) (ADVP (RB:[1333..1343] reversibly)) (VP (VBD:[1344..1351] blocked) (NP (NN:[1352..1359] channel) (NN:[1360..1368] activity)) (PP (IN:[1370..1372] in) (NP (NML (NN:[1373..1377] cell) (HYPH:[1377..1378] -) (VBN:[1378..1386] attached)) (NNS:[1387..1394] patches))) (PP (TO:[1395..1397] to) (NP (NP (QP (CD:[1398..1399] 4) (SYM:[1400..1403] +/-) (CD:[1404..1405] 1)) (NN:[1405..1406] %)) (PP (IN:[1407..1409] of) (NP (DT:[1410..1413] the) (NN:[1414..1421] control) (NN:[1422..1427] value))))) (,:[1427..1428] ,) (SBAR-ADV (IN:[1429..1436] whereas) (S (NP-SBJ (NML (CD:[1437..1439] 75) (NN:[1440..1442] nM)) (NN:[1444..1454] calphostin) (NN:[1455..1456] C)) (VP (VBD:[1457..1466] increased) (NP (DT:[1467..1470] the) (NN:[1471..1478] channel) (NN:[1479..1487] activity)) (PP (IN:[1488..1490] by) (NP-EXT (QP (CD:[1491..1494] 115) (SYM:[1495..1498] +/-) (CD:[1499..1501] 10)) (NN:[1501..1502] %))))))) (.:[1502..1503] .))) ;sentence 10 Span:1504..1603 ;Moreover, addition of 1 nM exogenous PKC reversibly and completely inhibited ;the 70-pS K+ channel. ;[1527..1528]:quantitative-value:"1" ;[1529..1531]:quantitative-units:"nM" ;[1542..1545]:substance:"PKC" ;[1592..1594]:substance:"K+" (SENT (S (ADVP (RB:[1504..1512] Moreover)) (,:[1512..1513] ,) (NP-SBJ (NP (NN:[1514..1522] addition)) (PP (IN:[1524..1526] of) (NP (NML (CD:[1527..1528] 1) (NN:[1529..1531] nM)) (JJ:[1532..1541] exogenous) (NN:[1542..1545] PKC)))) (ADVP (RB:[1546..1556] reversibly) (CC:[1557..1560] and) (RB:[1561..1571] completely)) (VP (VBD:[1572..1581] inhibited) (NP (DT:[1582..1585] the) (NML (CD:[1586..1588] 70) (HYPH:[1588..1589] -) (NN:[1589..1591] pS)) (NN:[1592..1594] K+) (NN:[1595..1602] channel))) (.:[1602..1603] .))) ;sentence 11 Span:1605..1955 ;However, inhibition of PKC with calphostin C (75 nM) only slightly prolonged ;the time course of the effect of Ca2+o on channel activity (370 +/- 40 s) ;and failed to abolish the inhibitory effect of 5 mM Ca2+o on channel ;activity in cell-attached patches, indicating that PKC was not mainly ;responsible for the effect of Ca2+o on channel activity. ;[1628..1631]:substance:"PKC" ;[1637..1649]:substance:"calphostin C" ;[1651..1653]:quantitative-value:"75" ;[1654..1656]:quantitative-units:"nM" ;[1716..1721]:substance:"Ca2+o" ;[1743..1753]:quantitative-value:"370 +/- 40" ;[1754..1755]:quantitative-units:"s" ;[1805..1806]:quantitative-value:"5" ;[1807..1809]:quantitative-units:"mM" ;[1810..1815]:substance:"Ca2+o" ;[1879..1882]:substance:"PKC" ;[1929..1934]:substance:"Ca2+o" (SENT (S (ADVP (RB:[1605..1612] However)) (,:[1612..1613] ,) (NP-SBJ-1 (NP (NN:[1614..1624] inhibition)) (PP (IN:[1625..1627] of) (NP (NN:[1628..1631] PKC))) (PP (IN:[1632..1636] with) (NP (NN:[1637..1647] calphostin) (NN:[1648..1649] C) (PRN (-LRB-:[1650..1651] -LRB-) (NP (CD:[1651..1653] 75) (NN:[1654..1656] nM)) (-RRB-:[1656..1657] -RRB-))))) (VP (VP (ADVP (RB:[1658..1662] only) (RB:[1663..1671] slightly)) (VBD:[1672..1681] prolonged) (NP (NP (DT:[1682..1685] the) (NN:[1687..1691] time) (NN:[1692..1698] course)) (PP (IN:[1699..1701] of) (NP (NP (DT:[1702..1705] the) (NN:[1706..1712] effect)) (PP (IN:[1713..1715] of) (NP (NN:[1716..1721] Ca2+o))) (PP (IN:[1722..1724] on) (NP (NN:[1725..1732] channel) (NN:[1733..1741] activity))))) (PRN (-LRB-:[1742..1743] -LRB-) (NP (QP (CD:[1743..1746] 370) (SYM:[1747..1750] +/-) (CD:[1751..1753] 40)) (NN:[1754..1755] s)) (-RRB-:[1755..1756] -RRB-)))) (CC:[1757..1760] and) (VP (VBD:[1761..1767] failed) (S (NP-SBJ-1 (-NONE-:[1767..1767] *)) (VP (TO:[1769..1771] to) (VP (VB:[1772..1779] abolish) (NP (NP (DT:[1780..1783] the) (JJ:[1784..1794] inhibitory) (NN:[1795..1801] effect)) (PP (IN:[1802..1804] of) (NP (NML (CD:[1805..1806] 5) (NN:[1807..1809] mM)) (NN:[1810..1815] Ca2+o))) (PP (IN:[1816..1818] on) (NP (NN:[1819..1826] channel) (NN:[1827..1835] activity)))) (PP-LOC (IN:[1836..1838] in) (NP (ADJP (NN:[1840..1844] cell) (HYPH:[1844..1845] -) (VBN:[1845..1853] attached)) (NNS:[1854..1861] patches))))))) (,:[1861..1862] ,) (S-ADV (NP-SBJ (-NONE-:[1862..1862] *)) (VP (VBG:[1863..1873] indicating) (SBAR (IN:[1874..1878] that) (S (NP-SBJ (NN:[1879..1882] PKC)) (VP (VBD:[1883..1886] was) (RB:[1887..1890] not) (ADJP-PRD (RB:[1891..1897] mainly) (JJ:[1898..1909] responsible) (PP (IN:[1910..1913] for) (NP (NP (DT:[1914..1917] the) (NN:[1919..1925] effect)) (PP (IN:[1926..1928] of) (NP (NN:[1929..1934] Ca2+o))) (PP (IN:[1935..1937] on) (NP (NN:[1938..1945] channel) (NN:[1946..1954] activity)))))))))))) (.:[1954..1955] .))) ;sentence 12 Span:1956..2216 ;In contrast, the effect of 5 mM Ca2+o on the apical 70-pS K+ channel was ;completely abolished when TAL tubules were first incubated in the ;17-octadecynoic acid (5 microM)-containing solution, an agent that ;specifically blocks cytochrome P-450 monooxygenase. ;[1983..1984]:quantitative-value:"5" ;[1985..1987]:quantitative-units:"mM" ;[1988..1993]:substance:"Ca2+o" ;[2015..2017]:substance:"K+" ;[2097..2117]:substance:"17-octadecynoic acid" ;[2119..2120]:quantitative-value:"5" ;[2121..2127]:quantitative-units:"microM" ;[2153..2158]:substance:"agent" ;[2185..2215]:cyp450:"cytochrome P-450 monooxygenase" (SENT (S (PP (IN:[1956..1958] In) (NP (NN:[1959..1967] contrast))) (,:[1967..1968] ,) (NP-SBJ-3 (NP (DT:[1969..1972] the) (NN:[1973..1979] effect)) (PP (IN:[1980..1982] of) (NP (NML (CD:[1983..1984] 5) (NN:[1985..1987] mM)) (NN:[1988..1993] Ca2+o))) (PP (IN:[1994..1996] on) (NP (DT:[1998..2001] the) (JJ:[2002..2008] apical) (NML (CD:[2009..2011] 70) (HYPH:[2011..2012] -) (NN:[2012..2014] pS)) (NN:[2015..2017] K+) (NN:[2018..2025] channel)))) (VP (VBD:[2026..2029] was) (ADVP (RB:[2030..2040] completely)) (VP (VBN:[2041..2050] abolished) (NP-3 (-NONE-:[2050..2050] *)) (SBAR-ADV (WHADVP-2 (WRB:[2051..2055] when)) (S (NP-SBJ (NN:[2056..2059] TAL) (NNS:[2060..2067] tubules)) (VP (VBD:[2068..2072] were) (ADVP-TMP (RB:[2073..2078] first)) (VP (VBN:[2080..2089] incubated) (PP-LOC (IN:[2090..2092] in) (NP (NP (DT:[2093..2096] the) (ADJP (NML (JJ:[2097..2112] 17-octadecynoic) (NN:[2113..2117] acid) (PRN (-LRB-:[2118..2119] -LRB-) (NP (CD:[2119..2120] 5) (NN:[2121..2127] microM)) (-RRB-:[2127..2128] -RRB-))) (HYPH:[2128..2129] -) (VBG:[2129..2139] containing)) (NN:[2140..2148] solution)) (,:[2148..2149] ,) (NP (NP (DT:[2150..2152] an) (NN:[2153..2158] agent)) (SBAR (WHNP-1 (WDT:[2160..2164] that)) (S (NP-SBJ-1 (-NONE-:[2164..2164] *T*)) (ADVP (RB:[2165..2177] specifically)) (VP (VBZ:[2178..2184] blocks) (NP (NML (NN:[2185..2195] cytochrome) (NN:[2196..2201] P-450)) (NN:[2202..2215] monooxygenase)))))))) (ADVP-TMP-2 (-NONE-:[2215..2215] *T*)))))))) (.:[2215..2216] .))) ;sentence 13 Span:2217..2440 ;In conclusion, these data indicate that Ca2+o is an important regulator of ;the apical 70-pS K+ channel and that a cytochrome P-450-dependent metabolite ;of arachidonic acid is involved in mediating this inhibitory effect. ;[2258..2263]:substance:"Ca2+o" ;[2310..2312]:substance:"K+" ;[2333..2349]:cyp450:"cytochrome P-450" ;[2360..2370]:substance:"metabolite" ;[2374..2390]:substance:"arachidonic acid" (SENT (S (PP (IN:[2217..2219] In) (NP (NN:[2220..2230] conclusion))) (,:[2230..2231] ,) (NP-SBJ (DT:[2232..2237] these) (NNS:[2239..2243] data)) (VP (VBP:[2244..2252] indicate) (SBAR (SBAR (IN:[2253..2257] that) (S (NP-SBJ (NN:[2258..2263] Ca2+o)) (VP (VBZ:[2264..2266] is) (NP-PRD (NP (DT:[2267..2269] an) (JJ:[2270..2279] important) (NN:[2280..2289] regulator)) (PP (IN:[2290..2292] of) (NP (DT:[2293..2296] the) (JJ:[2297..2303] apical) (NML (CD:[2304..2306] 70) (HYPH:[2306..2307] -) (NN:[2307..2309] pS)) (NN:[2310..2312] K+) (NN:[2314..2321] channel))))))) (CC:[2322..2325] and) (SBAR (IN:[2326..2330] that) (S (NP-SBJ-1 (NP (DT:[2331..2332] a) (ADJP (NML (NN:[2333..2343] cytochrome) (NN:[2344..2349] P-450)) (HYPH:[2349..2350] -) (JJ:[2350..2359] dependent)) (NN:[2360..2370] metabolite)) (PP (IN:[2371..2373] of) (NP (JJ:[2374..2385] arachidonic) (NN:[2386..2390] acid)))) (VP (VBZ:[2391..2393] is) (VP (VBN:[2395..2403] involved) (NP-1 (-NONE-:[2403..2403] *)) (PP-CLR (IN:[2404..2406] in) (S-NOM (NP-SBJ (-NONE-:[2406..2406] *)) (VP (VBG:[2407..2416] mediating) (NP (DT:[2417..2421] this) (JJ:[2422..2432] inhibitory) (NN:[2433..2439] effect))))))))))) (.:[2439..2440] .))) ;section 14 Span:2444..2488 ;PMID: 8760035 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2444..2448] PMID) (::[2448..2449] :) (CD:[2450..2457] 8760035) (NN:[2458..2459] -LSB-) (NNP:[2459..2465] PubMed) (::[2466..2467] -) (NN:[2468..2475] indexed) (IN:[2476..2479] for) (NNP:[2480..2488] MEDLINE-RSB-)))