$B@8M}3X8&5f=jG/Js(B $BG/JsL\<!$XLa$k(B$B@8M}8&%[!<%`%Z!<%8$X(B

6$B!%(BATP$B!&%"%G%N%7%s

2003$BG/(B8$B7n(B28$BF|!](B8$B7n(B29$BF|(B
$BBeI=!&@$OC?M!'0f>eOB=(!J9qN)0eLtIJ?)IJ1R@88&5f=j!K(B
$B=jFbBP1~pJs!K(B

$B!J#1!K(B
$B@T?qFbDK3PEAC#7O$K$*$1$k(BATP$B!&%"%G%N%7%s
$BCfDM1G@/(B1$B!$(BGu Jianguo2$B!$O+NO73(B 3$B!$F#ED0!H~(B3$B!$7'K\1I0l(B3$B!$(B$B5HB<7C(B1
$B!J(B1$B6e=#Bg3XBg3X1!E}9g@8M}3X!$(B2$B%U%m%j%@Bg3XG>8&5f=j!$(B3$B:42l0e2JBg3X?@7P@8M}3X!K(B
$B!J#2!K(B
$B3$GO?mBN:YK&$N6=J3@-@)8f$K$*$1$k(BATP$B$*$h$S%"%G%N%7%s
$B@nB<>-?N(B1$B!$2CF#AmIW(B2$B!J(B1$B;|7C0eBg!&LtM}3XBh(B1$B!$(B2$B;|7C0eBg!&?@7P@8M}!K(B
$B!J#3!K(B
$B%j%>%j%s;i
$B>>2,8y!$:4F#70(B$B!v(B$B!$>.Ln0Q@.!$LZB<=c;R!JJ!Eg0eBg!&0e!&LtM}!$Kc?l(B$B!v(B$B!K(B
$B!J#4!K(B
P2Y2$B
$BIY1J??6W(B1$B!$?9;3J~;R(B1$B!$HSEDF+;R(B1$B!$>.NS$-$_;R(B2$B!$ElCR9-(B1$B!$(B
$BB<;3F`H~;^(B1$B!$J!2,E/CK(B2$B!$0f>eOB=((B3, 4$B!$Ln8}8w0l(B2
$B!J(B1$B;0=EBg!&0e!&J,;R:YK&@8M}!$(B2$BJ<8K0eBg!&2rK6(B2$B!$(B3$B9qN)1R8&!&Be4$B6eBg1!!&Lt!K(B
$B!J#5!K(B
P2Y2$B
$B[Xt"Bg2p(B1,3$B!$>.@t=$0l(B2$B!$9B9xO/?M(B1,3$B!$DEED@?(B1$B!$=EK\!]:G>eM39aN$(B1$B!$0f>eOB=((B1,3

$B!J(B1$B9qN)1R8&!&Be2$B9qN)1R8&!&LtM}!$(B3$B6eBg1!!&Lt!&J,;R@)8f!K(B
$B!J#6!K(B
$B%R%HI=Hi%1%i%A%N%5%$%H$G2+ wave $B$O:YK&30(B ATP $B5Z$S(B P2Y2 $B
$BF#2<2CBe;R(B1$B!$>.@t=$0l(B2$B!$0f>e$+$*$j(B4$B!$:G>e!]=EK\$f$+$j(B1$B!$0f>eOB=((B1, 3
$B!J(B1$B9qN)1R8&!&Be2$BLtM}It!$(B3$B6e=#Bg3X!&1!!&Lt!&J,;R@)8f!$(B4$B;q@8F2%j%5!<%A%;%s%?!
$B!J#7!K(B
$B%^%&%9LVKl(BP2X$B
$B6bED!!@?(B1$B!$@P0f!!>!9%(B2$B!$?9Eg!!M[2p(B3$B!$@VLZ!!9*(B2$B!$C<@n!!JY(B2$B!$Cf@>!!=ECi(B3
$B!J(B1$B7D1~Bg@8M}!$(B2$BM}8&!&G>%;%s%?!3$B5~Bg1!!&@8BN>pJs2J3X!K(B
$B!J#8!K(B
$B;k:w>e3K$K$*$1$k(BATP$B1~Ez$H(BP2X$B
$B>eLn?-:H(B1$B!$;3ED=g;R(B2$B!$J!EDFXIW(B1,2
$B!J(B1$BIM>>0e2JBg3X@8M}Bh0l!$(B2$B@E2,Bg3XBg3X1!!&EE;R2J3X8&5f2J!&@8BV>pJs=hM}9V:B!K(B
$B!J#9!K(B
MNTB$B%K%e!<%m%s$K$*$1$k(BATP $B&C(B S$B$K$h$k<+H/$*$h$SM6H/%7%J%W%98eEEN.$KBP$9$k0[$J$k@)8f(B
$BLJLnCR0l(B1,2$B!$(BRichard J. Evans2$B!$(BIan D. Forsythe2
$B!J(B1$BJ!Eg0eBg!&0e!&LtM}!$(B2 Dept. of Cell Physiology & Pharmacology, Univ. of Leicester$B!K(B
$B!J(B10$B!K(B
ATP$B$*$h$S(BATP $B&C(BS$B$K$h$k(Bmonocyte chemoattractant protein-1 (MCP-1)
$B;:@8D4@a$K4X$9$kG>@ZJRG]M\7O$rMQ$$$?8!F$(B
$BJR;35.Gn!$0KF#H~@;!$Fn2mJ8!$:4F#8xF;!J5~Bg1!!&Lt!&@8BN5!G=2r@O3X!K(B
$B!J(B11$B!K(B
$BG]M\%i%C%HD24IJIFb?@7P:YK&$N(BATP$B$K$h$k:YK&Fb(BCa$BA}2CH?1~$N@- $B4XM?$9$k
$BB@ED(B $BMxCK!$5WJ]ED(B $B0+!$B<>e(B $B??DE9a!$259u(B $B7s0l!$0KF#(B $BLPCK!JKLBg!&1!!&=C0e!&LtM}!K(B
$B!J(B12$B!K(B
P2$B
$BHx>>K|N$;R!$>>1:!!Gn!J<"2l0eBg!&Bh(B2$B@8M}!K(B
$B!J(B13$B!K(B
ATP$BJ|=P2D;k2=$K$h$kJ|=P5!9=2r@O(B
$B8E2H4n;MIW(B1$B!$=)ED5WH~(B1$B!$2$B!$A>2fIt@5Gn(B1,2$B!J(B1$B2J5;CD!&:YK&NO3P!$(B2$BL>Bg1!!&0e!K(B
$B!J#P#1!K(B
$B%f%S%-%A%s(BC$BKvC
$B??;R9%@5(B1$B!$@a2HM}7C;R(B1,2$B!$]/0f>J2V;R(B1,2$B!$OBED7=;J(B2$B!$LnEDI4H~(B1
$B!J(B1$B6eBg1!!&Lt!$(B2$B9qN)@:!&?@%;!&?@7P8&!K(B
$B!J#P#2!K(B
P2Y$B
$BEDCfD>;R(B1$B!$G)@jF`H~9>(B1$B!$7&EDMN;R(B1$B!$dFEDCRH~(B1$B!$CfB<0l4p(B1$B!$(B
$B9b669,0l(B2$B!$66K\F;CK(B3$B!$9qM'!!>!(B1$B!$1
$B!JIp8K@n=w;RBg!&Lt!&(B1$BLtM}!$(B2$BLt:^!$(B3$BEg:,0eBg!&Bh0l@8M}!K(B
$B!J#P#3!K(B
PC12 $B:YK&$N(B ATP $B;:@8G=$K5Z$\$9%"%G%K%k;@%7%/%i!<%<$N(BP-$B%5%$%HAK32:^$N1F6A(B
$BF#?9W"9,!$K'@8=(8w!J@]FnBg3X!!Lt3XIt!!1R@8J,@O2=3X8&5f<
$B!J#P#4!K(B
P2Y12$B
$BB?ED70(B1$B!$>.@t=$0l(B1$B!$0f>eOB=((B2, 3$B!J9qN)1R8&!&(B1$BLtM}!$(B2$BBe3$B6eBg!&1!!&J,;R@)8f!K(B
$B!J#P#5!K(B
$B%_%/%m%0%j%"$K$*$1$k&A(B7$B%K%3%A%s@-%"%;%A%k%3%j%s7$B
$BNkLZCR5W(B1$B!$>>86L@Be(B1$B!$>>NS90L@(B2$B!$2$B!$=(!!OB@t(B1$B!$CgED5A7<(B1
$B!J9-Bg!&0e;uLtAm9g!!(B1$BLt8z2r@O!$(B2$B?@7P!&@:?@LtM}!K(B
$B!J#P#6!K(B
P2X7$B
$B7nK\8w=S!$86ED6Q!$8^==N$>4!$9bLZK.L@!J@E2,8)N)Bg!&Lt!K(B
$B!J#P#7!K(B
$B8IB+3K%7%J%W%9A0(BP2X$B
$BHKIZ1Q<#!$2CF#AmIW(B
$B!JEl5~;|7C2q0e2JBg3X!&Am9g0e2J3X8&5f%;%s%?!
$B!J#P#8!K(B
$B%7%J%W%9A0%"%G%N%7%s~(B
$BDE;aE5;R!$HKIZ1Q<#!$2CF#AmIW!J;|7C0eBg!!?@7P@8M}!K(B
$B!J#P#9!K%i%C%H4'=[4D$K$*$1$k%"%G%K%s%L%/%l%*%A%IBe
$B:4F#70(B$B#1(B$B!$>>2,8y(B$B#2(B$B!$LZB<=c;R(B$B#2(B$B!JJ!Eg0eBg!&0e!&(B$B#1(B$BKc?l2J!$(B$B#2(B$BLtM}!K(B
$B!J#P(B10$B!K%"%9%H%m%5%$%H$+$i$N<+H/E*(BATP$B$K$h$k:YK&Fb%7%0%J%kD4@a(B
$B>.@t=$0l(B1$B!$5\C]??M3H~(B2$B!$F#2<2CBe;R(B3$B!$0f>eOB=((B3,4
$B!J9qN)1R8&!&(B1$BLtM}!$(B3$BBe2$B@1Lt2JBg3X!$(B4$B6e=#Bg!&1!!&J,;R@)8f!K(B

$B!Z;22C![(B
$B0f>e(B $BOB=(!J9qN)1R8&!&Be>2,(B $B8y!$>.Ln(B $B0Q@.!$LJLn(B $BCR0l!JJ!Eg0eBg!&0e!&LtM}!K!$:4F#(B $B70!JJ!Eg0eBg!&0e!&Kc?l!K!$7':d(B $BCiB'!JJ!Eg0eBg!&0e!&?@7P@:?@!K!$EDB<(B $B@?;J!J;3G7Fb@=Lt!&LtM}Bh0l!K!$4X_7(B $B=SMN!$A0K\(B $BBvLi!JF#BtLtIJ!K!$6bED(B $B@?!J7D1~Bg!&@8M}!K!$@nB<(B $B>-?N!J;|7C0eBg!&LtM}(B1$B!K!$2CF#(B $BAmIW!$DE;a(B $BE5;R!$HKIZ(B $B1Q<#!$CSED(B $BN.@t(B $B=$0l!$F#2<(B $B2CBe;R!$B?ED(B $B70!J9qN)1R8&!&BeB<(B $BCRGn!JBgK2LtIJ!&AOLt%;%s%?!eLn(B $B?-:H!JIM>>0e2J!&@8M}!K!$7nK\(B $B8w=S!$86ED(B $B6Q!J@E2,8)N)Bg!&Lt!K!$8E2H(B $B4n;MIW!J2J5;CD!&:YK&NO3P!K!$Bg!K!$?\:j(B $B>0!JL>8E203X7]Bg!K!$>.@n(B $B?5;V!$2f1(B $B>!9@!J%U%!%$%6!!9,!$?y2,(B $BH~J]!JF`NI0eBg!&Bh0l@8M}!K!$Hx>>(B $BK|N$;R!J<"2l0eBg!&Bh(B2$B@8M}!K!$Fn!!2mJ8!$JR;3(B $B5.Gn!J5~ETBg!&Lt!&@8BN5!G=2r@O!K!$;T@n(B $B=c!J4X@>0eBg!&Bh(B2$B@8M}!K!$F#?9(B $BW"9,!J@]FnBg3X!&Lt3XIt!K!$5K9<(B $B=;R!$G)@j(B $BF`H~9>!JIp8K@n=w;RBg!&Lt!&LtM}!K!$CgED(B $B5A7>86(B $BL@Be!J9-Bg!&0e;uLt!&Lt8z2r@O!K!$CfDM(B $B1G@/!$1v@n(B $B9@51!J6e=#Bg3XBg3X1!E}9g@8M}3X!K!$??;R(B $B9%@5!$:4F#(B $B$"$f$_!J6e=#Bg!&1!!&Lt!K!$7KLZ(B $BLT!JJ!2,Bg!&0e!&LtM}!K!$@6?e(B $B=(Ci!J4p@88&!K!$:,K\(B $BCN8J!$;38*(B $BMU;R!$Lb;3(B $B=SI'!$0fK\(B $B7IFs!J@8M}8&!K(B

 

$B!J(B1$B!K@T?qFbDK3PEAC#7O$K$*$1$k(BATP$B!&%"%G%N%7%s

$B!!CfDM1G@/(B1$B!$(BGu Jianguo2$B!$O+NO73(B3$B!$F#ED0!H~(B3$B!$7'K\1I0l(B3$B!$(B$B5HB<7C(B1
$B!J(B1$B6e=#Bg3XBg3X1!E}9g@8M}3X!$(B2$B%U%m%j%@Bg3XG>8&5f=j!$(B3$B:42l0e2JBg3X?@7P@8M}3X!K(B

$B!!Kv>?$K$*$1$k463P>pJs$O0le9TO)$r7P$F9b0LCf?u$KEAC#$5$l$k!#@T?q8e3Q%l%Y%k$G$OMM!9$J?@7PEAC#J*?M3Mh$N463P>pJs$,=$>~$5$l$k$3$H$OCN$i$l$F$$$k$,!$6aG/!$@T?qFb$N(BATP P2X$BpJs$r=$>~$9$k$3$H$,L@$i$+$H$J$C$F$-$?!#$9$J$o$A!$(BATP P2X$B\:Y$rL@$i$+$K$9$k$?$a!$@T?q%9%i%$%9I8K\$rMQ$$$F@T?q8e3Q:YK&$+$i%Q%C%A%/%i%s%W5-O?$r9T$C$?!#@T?q8e3Q:YK&$OKv>?$+$i%0%k%?%_%s;@:nF0@-F~NO$r.6=J3@-%7%J%W%98eEEN.$NH/@8IQEY$OCxL@$KA}6/$7$?$3$H$+$i!$(BATP$BEjM?$K$h$C$F4Q;!$5$l$?:G=i$NA}6/8z2L$O(BATP P2X$B.6=J3@-%7%J%W%98eEEN.$NH/@8IQEY$O5U$K8:$C$F!$@T?qFb$K$*$$$F:YK&30(BATP$B$OD>@\E*$K%7%J%W%9A0$N(BP2X$Be$N7k2L$h$j!$@T?qDK3PEAC#7O$K$*$1$k(BATP$B$N:nMQ$O7P;~E*$JMWAG$rM-$9$kB?:L$J1F6A$r5Z$\$9$b$N$H?d;!$5$l$?!#(B

 

$B!J(B2$B!K3$GO?mBN:YK&$N6=J3@-@)8f$K$*$1$k(BATP
$B$*$h$S%"%G%N%7%s

$B!!@nB<>-?N(B1$B!$2CF#AmIW(B2$B!J(B1$B;|7C0eBg!&LtM}3XBh(B1$B!$(B2$B;|7C0eBg!&?@7P@8M}!K(B

$B!!:YK&30$KJ|=P$5$l$?%a%C%;%s%8%c!$N7O$G$O8+$i$l$J$$:YK&30(BATP$B$K$h$k%7%0%J%j%s%0$N%f%K!<%/$JFC@-$G$"$k$H9M$($i$l$k(B(Kato & Shigetomi, J. Physiol. 530:469-, 2001) $B!#(B

$B!!3$GO$O3Fe$GE,$7$?G>NNLn$G$"$k!#$7$+$7!$8=:_$^$G$NJ,;6G]M\$J$i$S$K5^@-C1N%I8K\$rMQ$$$?$3$l$i

$B!!$3$N$h$&$J(BATP-$B%"%G%N%7%s7O$N%$%s%?!<%W%l%$$NuCG%9%i%$%9I8K\(BCA3$B?mBN:YK&$+$i!$6=J3@-$*$h$SM^@)@-$N%7%J%W%9F~NO$r%Q%C%A%/%i%s%WK!$K$h$jF1;~5-O?$7!$(BATP$B$*$h$S%W%j%s/$5$;$?!#$3$N(B2$B$D$NAjH?$9$k:nMQ$O!$5-O?$5$l$??mBN:YK&(B22$BNcA4Nc$GF1;~$K4Q;!$5$l$?!#LtM}3XE*8!:w$K$h$C$F!$(BIPSC$B$NIQEYA}2C$O(B2meSATP$B$G6/$/3h@-2=$5$l(BPPADS$B$G/$O(BDPCPX$B$G1$B

$B!!0J>e$N7k2L$O!$:YK&30(BATP$B$,(B(1) P2X$B1$B/$H$$$&(B2$B$D$N0[$J$k8z2L$rF1;~$K0z$-5/$3$7F@$k$3$H$r<($9!#6=L#?<$$$3$H$K!$$3$l$i$N8z2L$O$$$:$l$b?mBN:YK&$N6=J3@-$rDc2<$5$;$k!#(BATP$B$O(B1$B$D$NJ,;R$G$"$j$J$,$i!$(BATP$B$l9gL\E*$K3h@-2=$7!$?@7P%M%C%H%o!<%/$N6=J3@-$r6(F/E*$K@)8f$7F@$k$H9M$($i$l$k!#(B

 

$B!J(B3$B!K%j%>%j%s;i

$B!!>>2,8y!$:4F#70(B$B!v(B$B!$>.Ln0Q@.!$LZB<=c;R!JJ!Eg0eBg!&0e!&LtM}!$Kc?l(B$B!v(B$B!K(B

$B!!:YK&30$N(BATP$BBepJsJQ49$K=EMW$JLr3d$r2L$?$7$F$$$k!#:G6a!$1j>I$d5u7lIBJQ$K$$$*$F(Becto-nucleotidase$B3h@-$NJQ2=$r<($9@.@S$,Js9p$5$l$F$$$k!#$^$?!$7l>.HD$dFbHi:YK&$+$iJ|=P$5$l$k(BATP$B$d(BADP$B$NJ,2r$,>c32$5$l$k$H=[4D4o7O>c32$N860x$K$J$k$3$H$bL@$i$+$K$5$l$F$$$k!#$7$+$7!$$I$N$h$&$J5!=x$G(BATP$BBeo$KP6?J$7!$BgNL$N%j%>%j%s;i%j%s;i%[%9%U%!%A%8%k%3%j%s(B(LPC) $B$K$h$jG;EY0MB8E*$KA}Bg$7$?!#$3$N(BLPC$B$K$h$k(BATP$BJ,2r3h@-$NP6?J$O!$3&LL3h@-:^$H$7$F:YK&KlF)2a@-$rP6?J$5$;$k(BLPC$B$N:nMQ$h$jDcG;EY$GG'$a$i$l$?!#$^$?!$(BATP$B$NJ,2r3h@-$KHf$Y!$(BAMP$B$NJ,2r3h@-$X$N1F6A$O>.$5$+$C$?!#(BLPC$B$N(BATP$BJ,2r3h@-P6?J:nMQ$O(Becto-nucleotide triphophate diphophohydrolase 1 (E-NTPDase 1, ecto-apyrase) $B$rH/8=$5$;$?(BHEK293$B:YK&$G$b:F8=$5$l$?!#$3$N:YK&$rMQ$$$FB&:?$N;iKC;@$,0[$J$k$N%j%s;i%[%9%U%!%A%8%k%;%j%s!$%j%>%[%9%U%!%A%8%k%$%N%7%H!<%k$K$O:nMQ$,G'$a$i$l$?$,!$%j%>%[%9%U%!%A%8%s;@!$%9%U%#%s%4%7%s(B-1-$B%j%s;@$OL58z$G$"$C$?!#$5$i$K!$(BLPC$B$r=hM}$7$?:YK&$G$O9ZAG3h@-$,H?1~1UCf$KM7N%$7!$(BLPC$B$r@v>t$7$?8e$G$O:YK&$N(Becto-NTPDase1$B3h@-$,Dc2<$7$F$$$?!#0J>e$N7k2L$+$i!$5u7l?4$GG'$a$i$l$?(BATP$BJ,2r9ZAG$NM7N%$O?4B!Fb$G;:@8$5$l$k%j%>%j%s;i

 

$B!J(B4$B!K(BP2Y2$B

$B!!IY1J??6W(B1$B!$?9;3J~;R(B1$B!$HSEDF+;R(B1$B!$>.NS$-$_;R(B2$B!$ElCR9-(B1$B!$(B
$BB<;3F`H~;^(B1$B!$J!2,E/CK(B2$B!$0f>eOB=((B3, 4$B!$Ln8}8w0l(B2
$B!J(B1$B;0=EBg!&0e!&J,;R:YK&@8M}!$(B2$BJ<8K0eBg!&2rK6(B2$B!$(B3$B9qN)1R8&!&Be4$B6eBg1!!&Lt!K(B

$B!!0JA0!$K\8&5f2q$G!$(BHEK293$B:YK&$KH/8=$7$?%+%W%5%$%7%s\:Y$J8!F$$r9T$C$?!#@h$:!$@82=3XE*$J@\(BPKC$B$K$h$C$F%j%s;@2=$5$l$k$3$H$r>ZL@$7$?!#E@JQ0[BN$rMQ$$$?EE5$@8M}3XE*5!G=2r@O$+$i!$(BTRPV1$B$N:YK&Fb%I%a%$%s$N(BPKC$B$K$h$C$F%j%s;@2=$5$l$k(B2$B$D$N%;%j%s;D4p$rF1Dj$7$?!#$3$l$i$N%;%j%s;D4p$r%"%i%K%s$KCV49$7$?JQ0[BN$G$O!$(BATP$B$K$h$k(BTRPV1$B$N%+%W%5%$%7%s3h@-2=EEN.$NA}Bg$,$_$i$l$J$$$N$_$J$i$:!$Ln@87?$G$O4Q;!$5$l$k3h@-2=29EYogCM$NDc2<$bG'$a$i$l$J$+$C$?!#$3$N%a%+%K%:%`$N=EMW@-$r8DBN%l%Y%k$G8!>Z$9$k$?$a$K!$(BATP$BEjM?$K$h$kG.@-DK3P2aIR$r%^%&%9$G4Q;!$7$?!#Ln@87?%^%&%9$G$O!$(BATP$B$NB-DlEjM?$K$h$C$FCx$7$$G.@-DK3P2aIR$,G'$a$i$l$?$,!$(BTRPV1$B7gB;%^%&%9$G$O!$$=$N$h$&$JDK3P2aIR$OA4$/$_$i$l$J$+$C$?!#8DBN%l%Y%k$K$*$$$F!$(BATP$B$H(BTRPV1$B$N5!G=O"4X$,L@$i$+$K$J$C$?!#6C$/$Y$-$3$H$K!$(BP2Y1$B7gB;%^%&%9$G$bLn@87?$HF1MM$NDK3P2aIR$,4Q;!$5$l!$%^%&%9$K$*$$$F$O(BP2Y1$Be$N8!F$$+$i!$%^%&%9$K$*$$$F$O!$=}32;~$K:YK&30$KJ|=P$5$l$k(BATP, UTP$B$K$h$C$F(BP2Y2$B

 

$B!J(B5$B!K(BP2Y2$B

$B!![Xt"Bg2p(B1,3, $B>.@t=$0l(B2, $B9B9xO/?M(B1,3, $BDEED@?(B1,$B!!=EK\!]:G>eM39aN$(B1, $B0f>eOB=((B1,3
$B!J(B1$B9qN)1R8&!&Be2$B9qN)1R8&!&LtM}!$(B3$B6eBg1!!&Lt!&J,;R@)8f!K(B

$B!!(BATP$B$OCN3P?@7P$K$*$$$F%$%*%s%A%c%M%kFbB"7?(BP2X$B\:Y$J8&5f$r9T$C$?!#@h$:(BCa2+$B%$%a!<%8%s%0(B(fura-2$BK!(B) $B$K$h$j!$B?$/$N>.7?$+$D%+%W%5%$%7%s46C<:$7$?!#(BUTP$B$K$h$j0z$-5/$3$5$l$k%"%m%G%#%K%"$O&A&B(BmeATP$B$K$h$jM6H/$5$l$k$=$l$h$j$bD9;~4V;}B3$7$?!#&A&B(BmeATP$B$H0[$J$j!$(BUTP$B$K$h$je!$>.7?$G%+%W%5%$%7%s46

 

$B!J(B6$B!K%R%HI=Hi%1%i%A%N%5%$%H$G2+ wave$B$O:YK&30(BATP$B5Z$S(BP2Y2$B

$B!!F#2<2CBe;R(B1$B!$>.@t=$0l(B2$B!$0f>e$+$*$j(B4$B!$:G>e!]=EK\$f$+$j(B1$B!$0f>eOB=((B1, 3
$B!J(B1$B9qN)1R8&!&Be2$BLtM}It!$(B3$B6e=#Bg3X!&1!!&Lt!&J,;R@)8f!$(B4$B;q@8F2%j%5!<%A%;%s%?!

$B!!HiIf$O!$?HBN$N9-$$HO0O$r@j$a$F$*$j!$4%Ag!$2=3XJ*Ho$KGx$5$l$F$$$k$@$1$G$J$/!$B;=}$d1j>I@-<@45!$%"%l%k%.!2+$BG;EY$rJQ2=$5$;$k!#(BCa2+$B$OHiIf$N:G30It$K$"$?$kI=Hi$N91>o@-0];}$K=EMW$G$"$j!$I=Hi3Q2=:YK&$NA}?#$HJ,2=$N%P%i%s%9$r@)8f$7$F$$$k!#(BATP$B$O?tB?$/$N:YK&$K$*$$$F!$:YK&4V>pJsEAC#J*o%R%HI=Hi3Q2=:YK&(B(Normal Human Epidermal Keratinocytes: NHEKs) $B$NC10lG]M\7O5Z$S!$%^%&%98e:,?@7P@a(B(DRG) $B?@7P:YK&$H$N6&G]M\7O$rMQ$$$F!$:YK&30(BATP$B$K$h$jG^2p$5$l$k(BCa2+ wave$B$NEAGE$K$D$$$F8!F$$r9T$J$C$?!#LtM}3XE*2r@O$N7k2L!$(BNHEKs$B$O5!G=E*$JBe2+$BG;EY(B([Ca2+]i) $B$N>e>:$,8+$i$l!$B3$$$F:YK&30(BATP$B0MB8E*$K<~0O$N(BNHEKs $B$X(BCa2+ wave$B$NEAGE$,3NG'$5$l$?!#(BLuciferin-luciferase$BK!$K4p$E$/(BATP$B%$%a!<%8%s%02r@O$K$h$j!$(BNHEKs$B$+$i;I7c0MB8E*$J(BATP$B$NJ|=P5Z$S3H;6$,4Q;!$5$l$?!#(BDRG$B?@7P:YK&$O!$I=Hi$N4pDl:YK&AX$K$=$NKvC<$r1d$P$7$F$$$k$3$H$,CN$i$l$F$$$k!#(BNHEKs$B$H(BDRG$B?@7P:YK&$N6&G]M\7O$K$*$$$F$b!$(BNHEKs$B$G5!3#;I7c$K$h$j2+ wave$B$,!$:YK&30(BATP$B5Z$S(BP2Y2$B2+]i$B$r>e>:$5$;$?!#$3$N$3$H$+$i!$:YK&30(BATP$B$O(BNHEKs$B$K$*$$$F:YK&4V(BCa2+ wave$B$r7A@.$9$kpJsEAC#J*

 

$B!J(B7$B!K%^%&%9LVKl(BP2X$B

$B!!6bED!!@?(B1$B!$@P0f!!>!9%(B2$B!$?9Eg!!M[2p(B3$B!$@VLZ!!9*(B2$B!$C<@n!!JY(B2$B!$Cf@>!!=ECi(B3
$B!J(B1$B7D1~Bg@8M}!$(B2$BM}8&!&G>%;%s%?!3$B5~Bg1!!&@8BN>pJs2J3X!K(B

$B!!:YK&30(BATP$B$OLVKl?@7PEAC#J*uAX$N6-3&ItIU6a$KE@>u$KJ,I[$9$kM[@-=j8+$,4Q;!$5$l$?!#(BP2X2$BuAX$N%5%V%i%_%J(Ba$B$G6/$$LH1VH?1~M[@-A|$,4Q;!$5$l$?!#(BP2X4$BK;RBNB&$H6/KlB&$KB8:_$7$F$$$?!#(BP2X2$B$NLH1VH?1~$O%3%j%s:nF0@-%K%e!<%m%s$N%^!<%+!<$G$"$k(BChAT$B$NLH1VH?1~$H0lCW$7$?!#$^$?(BP2X2$B$NLH1VH?1~$O%3%j%s:nF0@-%K%e!<%m%s$K(BGFP$B%7%0%J%k$rH/8=$9$k(Btransgenic mouse$B$K$*$$$F$b0lCW$7$?!#(BTransgenic mouse$B$K(BIMCT$B$rMQ$$$F%3%j%s:nF0@-%K%e!<%m%s$rA*BrE*$K:YK&;`$5$;$k$H!$(BGFP$B%7%0%J%k$,>C<:$7$?NN0h$N$_$G(BP2X2$B$NLH1VH?1~$,>C<:$7$?!#$3$N$3$H$+$i(BP2X2$B$NLH1VH?1~$O(Bstarburst$B%"%^%/%j%s:YK&$NuFM5/>e$KA*BrE*$KH/8=$7$F$$$k$b$N$H9M$($i$l$k!#0J>e$N7k2L$+$i!$(BP2X2$B

 

$B!J(B8$B!K;k:w>e3K$K$*$1$k(BATP$B1~Ez$H(BP2X$B

$B!!>eLn?-:H(B1$B!$;3ED=g;R(B2$B!$J!EDFXIW(B1,2
$B!J(B1$BIM>>0e2JBg3X@8M}Bh0l!$(B2$B@E2,Bg3XBg3X1!!&EE;R2J3X8&5f2J!&@8BV>pJs=hM}9V:B!K(B

$B!!;k:w>e3K$O!$%*%-%7%H%7%s!$%P%>%W%l%C%7%s$r2e3K$N?@7P:YK&$K!$%9%i%$%9%Q%C%AK!$rE,MQ$7!$(BATP$BEjM?$K$h$kH?1~$r5-O?$7$?!#EEN.8GDj2=$K$*$$$F!$(BATP$BEjM?$K$h$kC&J,6K$*$h$S!$3hF0EE0L$NH/@8$,4Q;!$5$l!$EjM?8e$K$O<+H/H/2PIQEY$NDc2<$,4Q;!$5$l$?!#$^$?!$EE0L8GDj2=!JJ];}EE0L(B-50mV$B!K$K$*$$$F!$(BATP$BEjM?$K$h$C$FFb8~$-EEN.$N$_$J$i$:!$EjM?8e$K308~$-EEN.@.J,$,4Q;!$5$l$?!#$3$NFb8~$-EEN.@.J,$O(BPPADS$B$K$h$C$FM^@)$5$l$?!#(BATP 1 mM$BB8:_2<$G$NEE05(B-$BEEN.6J@~$O!$Fb8~$-@0N.:nMQ$,8+$i$l$?!#%9%i%$%9%Q%C%A$G4Q;!$5$l$?EEN.$O$9$Y$F!$CY$$IT3h@-2=2aDx$r;}$D$b$N$G$"$j!$5!3#E*C1N%$K$h$C$F4Q;!$5$l$?Aa$$IT3h@-2=2aDx$r;}$D$b$N$O8+$i$l$J$+$C$?!#$^$?!$&A&B(Bmethylen ATP$BEjM?$K$h$C$F$bFb8~$-EEN.$re3K?@7P:YK&BN$K$*$$$F!$(BP2X2$B%5%V%?%$%W$r

 

$B!J(B9$B!K(BMNTB$B%K%e!<%m%s$K$*$1$k(BATP$B&C(BS$B$K$h$k<+H/$*$h$SM6H/%7%J%W%98eEEN.$KBP$9$k0[$J$k@)8f(B

$BLJLnCR0l(B1,2$B!$(BRichard J. Evans2$B!$(BIan D. Forsythe2
$B!J(B1$BJ!Eg0eBg!&0e!&LtM}!$(B2 Dept. of Cell Physiology & Pharmacology, Univ. of Leicester$B!K(B

$B!!(BMedial nucleus of the trapezoid body (MNTB) $B$OG>44$K$*$$$F2;8;Dj0L$K4X$o$kD03PCf7Q$K=EMW$JF/$-$r$7$F$$$k?@7P$G$"$k!#2f!9$O(BMNTB$B%K%e!<%m%s$K$*$$$F!$%W%j%s44$h$j(B170-200 $B&L(Bm$B$N%9%i%$%9$r:n@.$7!$%[!<%k%;%k%Q%C%A%/%i%s%WK!$K$h$jEEN.$r5-O?$7$?!#(BMNTB$B%K%e!<%m%s$G$O6=J3@-(B(sEPSC) $B$*$h$SM^@)@-(B(sIPSC) $B<+H/%7%J%W%98eEEN.$,4Q;!$5$l$k$,!$(BP2$BC<:$7$?$3$H$h$j!$?@7P=*Kv$*$h$S:YK&BN$N0[$J$k(BP2X$BC<:$5$;$?!#$3$l$i$N$3$H$h$j!$$3$l$i$N(BP2$B%"%4%K%9%H$NM6H/%7%J%W%98eEEN.M^@):nMQ$O<+H/E*%7%J%W%98eEEN.$KBP$9$k@)8f$H0[$J$j(Badenosine A1 $B@\(Badenosine$B$KJ,2r$5$l$k$?$a$J$N$+!$%0%j%"$"$k$$$O?@7P$J$I$+$i$N(BATP$B$NM7N%$r2p$9$k$b$N$G$"$k$+$OL@$i$+$K$J$C$F$*$i$::#8e$N8!F$2]Bj$G$"$k!#(B

 

$B!J(B10$B!K(BATP$B$*$h$S(BATP$B&C(BS$B$K$h$k(Bmonocyte chemoattractant protein-1 (MCP-1) $B;:@8D4@a$K4X$9$kG>@ZJRG]M\7O$rMQ$$$?8!F$(B

$B!!JR;35.Gn!$0KF#H~@;!$Fn2mJ8!$:4F#8xF;!J5~Bg1!!&Lt!&@8BN5!G=2r@O3X!K(B

$B!!G>AH?%@ZJRG]M\7O$O!$:YK&9=C[$d8D!9$N:YK&$N3h@-2=>uBV$,J,;6G]M\7O$HHf3S$7$F$h$j(Bin vivo$B$K6a$$>uBV$K$"$k$?$a!$3h@-2=>uBV$N0c$$$,:YK&$NH?1~@-$rBg$-$/:81&$9$k%0%j%":YK&$N8&5f$KHs>o$KM-MQ$G$"$k$H9M$($i$l$k!#K\8&5f$G$O!$(BATP$B$*$h$S$=$NHs?e2r@-%"%J%m%0(BATP$B&C(BS$B$N(BMCP-1$B$N;:@8!&M7N%$KBP$9$k8z2L$K$D$$$F!$$3$NG>@ZJRG]M\7O$rMQ$$$F8!F$$r9T$C$?!#(B

$B!!@88e(B2-3$BF|Np%i%C%H$NBgG>HirBNNN0h$+$i4'>u@ZJR!J(B300$B&L(BM$B8|!K$r:n@=$7!$(B10-11$BF|4V@ECV3&LLG]M\8e!$

$B!!(BATP$B$"$k$$$O(BATP$B&C(BS$B=hCV$K$h$j!$G;EY0MB8E*$JG]COCf$X$N(BMCP-1$B$NM7N%$,4Q;!$5$l$?!#$=$N;:@8$N%?%$%`%3!<%9$O!$(BATP$B$"$k$$$O(BATP$B&C(BS$B!J$H$b$K(B300 $B&L(BM$B!K(B3$B;~4V=hCV$K$h$j!$=hCV3+;O8e(B1$B;~4V$G4{$K4Q;!$5$l!$=hCV3+;O8e(B3-4$B;~4V$r%T!<%/$H$9$k0l2a@-$N$b$N$G$"$C$?!#$^$?!$$=$N

$B!!0J>e$N7k2L$h$j!$G>AH?%@ZJRG]M\7O$K$*$$$F(BATP$B$"$k$$$O(BATP$B&C(BS$B$O!$%"%9%H%m%5%$%H$G$N(BMCP-1$B$N;:@8!&M7N%$r/$J$/$H$b0lIt$K$O0[$J$k%5%V%?%$%W$N%W%j%s=hCV$H$b$K(BERK$B$*$h$S(BJNK$B%-%J!<%<$OB%?JE*$K!$5U$K(Bp38MAP $B%-%J!<%<$OM^@)E*$K$=$l$>$l4XM?$7$F$$$k$3$H$,<(:6$5$l$k!#(B

 

$B!J(B11$B!KG]M\%i%C%HD24IJIFb?@7P:YK&$N(BATP$B$K$h$k:YK&Fb(BCa$BA}2CH?1~$N@-

$B!!B@EDMxCK!$5WJ]ED0+!$B<>e??DE9a!$259u7s0l!$0KF#LPCK!JKLBg!&1!!&=C0e!&LtM}!K(B

$B!!(BATP$B$OD24IJIFb?@7P$K$*$$$FB.$$6=J3@-%7%J%W%98eEE0L$r7A@.$9$k?@7PEAC#J*2+]i) $B$r(Bfura-2$B%l%7%*2hA|2r@OK!$K$h$jB,Dj$7!$(B[Ca2+]i$BA}2CH?1~$N@-2$B2+]i$BA}2C$O?@7PFC0[CAGr(BPGP9.5$B93BNM[@-:YK&$N$_$G@8$8$?$3$H$+$i!$K\H?1~$,@8$8$k:YK&$r?@7P:YK&$H$7$F5!G=E*$KF1Dj$7$?!#(B

$B!!(BATP$B$OJIFb?@7P:YK&$K$*$$$FG;EY0MB8@-(B(0.3$B!A(B100$B&L(BM) $B$K(B[Ca2+]i$BA}2CH?1~$r0z$-5/$3$7$?!#$3$NH?1~$O301U(BCa2+$B=|5n$K$h$jBg$-$/M^@)$7$?!#(BATP$B$K$h$k(B[Ca2+]i$BA}2CH?1~$OEE0L0MB8@-(BCa$B%A%c%M%kEE0L$,(B0mV$B$NIT3h2=$NCY$$Fb8~$-EEN.$r0z$-5/$3$7$?!#(BP2$B2+]i$BA}2C5Z$SFb8~$-EEN.H?1~$r2D5UE*$KM^@)$7$?!#(BP2$B2+]i$BA}2C$NNO2A=g$O(BATP$B!f(BATP$B&C(BS$B!d(BCTP$B!f(B2MeSATP$B!d(BBzATP$B!J&A(B,$B&B(B-MeATP $B$OL58z!K$G$"$C$?!#(BATP$B$K$h$kFb8~$-EEN.$ODcG;EY(B(0.2$B!A(B200 $B&L(BM)$B$N(BZn2+$B!$(BCu2+$B!$(BCd2+$B$K$h$jA}6/$5$l$?!#$^$?!$(BATP$BEEN.$O(BpH6.6$B$G$OLs(B3$BG\$KA}Bg$7!$5U$K(BpH8$B$G$OLs(B30%$B$K8:>/$7$?!#(BRT-PCR$B$K$h$j%i%C%HD24IJIFb?@7P:YK&$K(BP2X2$B!$(BP2X4$B!$(BP2X5$B$N(BmRNA$B$,8!=P$5$l$?!#93(BP2X4$B93BN$K$h$kLH1V@w?'$GM[@-:YK&$,8!=P$5$l!$$3$N:YK&$G$N(BP2$B3h@-2=Lt$NNO2A=g$b>e5-$H0lCW$7$?!#(B

$B!!K\2+]i$BA}2CH?1~$O4$B$G$"$k$3$H$,<(:6$5$l$?!#(B

 

$B!J(B12$B!K(BP2$B

$B!!Hx>>K|N$;R!$>>1:!!Gn!J<"2l0eBg!&Bh(B2$B@8M}!K(B

$B!!%^%&%9B[;yM3MhA06n;iKC:YK&(B3T3-L1$B$O!$;iKC:YK&J,2=$N%b%G%k$H$7$F:G$b$h$/8&5f$5$l$F$$$kG]M\3t:YK&$N0l$D$G$"$k!#(B3T3-L1$B:YK&$,=*KvJ,2=$K0\9T$9$k$?$a$K$O:YK&<~4|$,(BG0/G1$B$GDd;_$9$k$3$H$,I,MW$G$"$j!$DL>o$NG]M\c32$K$h$j:YK&<~4|$rDd;_$7$?8e!$(Bdexamethasone$B!$(B1-methyl-3-isoxanthine$B5Z$S(Binsulin$B$rJ,2=M6F30x;R$H$7$F2C$($k$3$H$K$h$C$F@.=O;iKC:YK&$KJ,2=$5$;$kJ}K!$,:G$bI8=`E*$JuBV$G$bLt:^$K$h$C$F:YK&<~4|$rDd;_$5$;$k$HJ,2=M6F32DG=$G$"$k$H$$$&Js9p$,$"$k$3$H$+$i!$:YK&<~4|$,(BG0/G1$B$GDd;_$9$k$3$H$,=EMW$G$"$k$H9M$($i$l$F$$$k!#(B

$B!!2f!9$O!$L$J,2=(B3T3-L1$B:YK&$K$*$1$k:YK&9|3J$H:YK&1?F0$K$D$$$FD4$Y$?$H$3$m!$A}?#Cf$N:YK&$K$O%"%/%A%s%9%H%l%9%U%!%$%P!<$,H/C#$7$F$$$k$,!$%3%s%U%k%(%s%H$KC#$9$k$H%9%H%l%9%U%!%$%P!<$O>C<:$7!$:YK&Kl6aJU$K%"%/%A%s$,=8@Q$9$k$3$H!$A}?#Cf$N:YK&$K$*$$$F:YK&30(BATP$B$O%9%H%l%9%U%!%$%P!<$r2u$7$F:YK&Kl<~JU$KFC0[E*$K%"%/%A%s$r:F9=C[$7!$%i%C%U%j%s%0$d;e>u2>B-$K$h$kCx$7$$:YK&7ABV$NJQ2=$r0z$-5/$3$9$3$H!$5Z$S!$Ls(B30%$B$NDc$$:YK&L)EY$N:YK&$K(BATP$B$rM?$($F%$%s%-%e%Y!<%7%g%s$7$?8e$KJ,2=M6F30x;R$r2C$($k$H!$A}?#$rB3$1$J$,$i@.=O;iKC:YK&$KJ,2=$9$k$3$H!$$r8+=P$7$?!#$3$l$i$N8z2L$O(BP2$B

 

$B!J(B13$B!K(BATP$BJ|=P2D;k2=$K$h$kJ|=P5!9=2r@O(B

$B!!8E2H4n;MIW(B1$B!$=)ED5WH~(B1$B!$2$B!$A>2fIt@5Gn(B1,2
$B!J(B1$B2J5;CD!&:YK&NO3P!$(B2$BL>Bg1!!&0e!K(B

$B!!IaJWE*$J:YK&Fb>pJsEAC#J*l$O0[$J$k$,!$:YK&30(BATP$B$OIaJWE*$J:YK&30>pJsEAC#J*/$J$/$H$b(B2$Be$N0[$J$C$?(BATP$BJ|=P7PO)$,4XM?$7$F$$$k$3$H$,<(:6$5$l$?!#(BL-L$B$rMQ$$$?J|=P(BATP$B$N%$%a!<%8%s%0Ey:G?7$N7k2L$+$i$=$N7PO)$K$D$$$F5DO@$9$k!#(BATP$BJ|=P7PO)$O$$$o$P%+%k%7%&%`%7%0%J%j%s%0$K$*$1$k%+%k%7%&%`%A%c%s%M%k$KAjEv$7$F$*$j!$$=$N5!=x$O=EMW$G$"$j!$B?

 

$B!J(BP1$B!K%f%S%-%A%s(BC$BKvC

$B!!??;R9%@5(B1$B!$@a2HM}7C;R(B1,2$B!$]/0f>J2V;R(B1,2$B!$OBED7=;J(B2$B!$LnEDI4H~(B1
$B!J(B1$B6eBg1!!&Lt!$(B2$B9qN)@:!&?@%;!&?@7P8&!K(B

$B!!(BUCH L1$B$O%(%M%k%.!<0MB8E*$J%?%s%Q%/o$K$h$kG>5!G=>c32$b$$$/$D$+Js9p$5$l$F$$$k!#2f!9$O@$3&$K@h6n$1$F(Bgad (gracile axonal dystrophy) $B%^%&%9$,(BUCH L1$B$N5!G=AS<:$rM-$9$k?@7PJQ@-%b%G%k$G$"$k$3$H$r<($7?@7P:YK&$K$*$$$F%f%S%-%A%s%l%Y%k$,Dc2<$7$F$$$k$3$H$r8+$$$@$7$?!#%"%a%U%i%7$K$*$$$F$O(BUCH L1$B$HAjF1@-$N9b$$(BUCH$B$,3X=,$H5-21$K=EMW$G$"$k$3$H$,Js9p$5$l$F$$$k$,!$S.F}N`$G$N?@7P2sO)5!G=$K$*$1$k(BUCH L1$B$NLr3d$O$$$^$@2rL@$5$l$F$$$J$$!#$=$3$G!$K\8&5f$G$O?@7PEAC#$K$*$1$k(BUCH L1$B$N:nMQ$K$D$$$F8!F$$9$k$3$H$K$7$?!#:#2s!$?@7PEAC#J*$N%W%m%F%$%s%-%J!<%<$K$O0MB8$7$J$+$C$?!#$5$i$K!$(BPC12 Tet-Off$B:YK&$K%I!<%Q%_%s$K$h$j@)8f$5$l$k%j%s;@2=CAGr(BDARPP-32$B$,H/8=$7$F$$$k$3$H$rDjNLE*(BRT-PCR$B$K$h$j3NG'$7!$(BDARPP-32$B$N%j%s;@2=$H(BPKA$B!$(BCDK5$B$N@)8f$,$I$N$h$&$K(BP2X$B

 

$B!J(BP2$B!K(BP2Y$B

$B!!EDCfD>;R(B1$B!$G)@jF`H~9>(B1$B!$7&EDMN;R(B1$B!$dFEDCRH~(B1$B!$CfB<0l4p(B1$B!$(B
$B9b669,0l(B2$B!$66K\F;CK(B3$B!$9qM'!!>!(B1$B!$1$B!!(B
$B!JIp8K@n=w;RBg!&Lt!&(B1$BLtM}!$(B2$BLt:^!$(B3$BEg:,0eBg!&Bh0l@8M}!K(B

$B!!!ZL\E*![2f!9$O!$Dc?;F)05>uBV2<$GA}Bg$7$?7l4IFbHi:YK&MF@Q$N=$I|5!9=!JD4@a@-BN@Q8:>/5!9=!'(BRVD$B!K$KBP$7!$Fb0x@-$N(BATP$B$,B%?JE*$K4XM?$9$k$3$H!$$5$i$KEy?;F)05>uBV2<$K$*$$$F$b!$(BATP$B$,(BP2Y$B/:nMQ$rM-$9$k$3$H$rJs9p$7$F$-$?(B1) $B!#:#2s$O!$(BATP$B$N@8M}E*Lr3d$r99$KL@$i$+$K$9$k$?$a$K!$:YK&LL@Q8:>/:nMQ$H:YK&AXF)2a@-$H$N4XO"@-$K$D$$$F8!F$$7$?!#(B

$B!!!ZJ}K!![2+]I) $B$O(BCalcium Green-1-AM$B$r;X<(Lt$H$7$F6&>GE@%l!<%6!<82Hy6@!&2hA|2r@OAuCV$rMQ$$$FB,Dj!$:YK&MF@Q$O82Hy6@2hA|$h$jF@$i$l$?:YK&LL@Q$r(BNIH Image$B$G?tCM2=$7$F$=$N;XI8$H$7$?!#:YK&AX$NF)2a@-$O!$FbHi:YK&AX$rF)2a$7$?(BFITC-labeled dextran (FD-4) $BNL$r;XI8$H$7$F8!F$$7$?!#$5$i$K!$%i%C%HHxIt^uN.I8K\$rMQ$$$F!$HxItI=AX$XF)2a$7$?(BFD-4$B$r6&>GE@%l!<%6!<82Hy6@$K$FB,Dj$7$?!#(B

$B!!!Z7k2L![(B1) 2meS-ATP$B$H(BADP$B!$$5$i$K(BUTP$B$O:YK&LL@Q$rM-0U$K8:>/$5$;$k$H$H$b$K!$(B[Ca2+]i$B$rM-0U$K>e>:$5$;$?!#(B2) 2meS-ATP$B$K$h$k:YK&LL@Q$N8:>/$*$h$S(B [Ca2+]i$B$N>e>:$O(BP2Y$B2+$B%9%H%"8O3iLt$N(Bthapsigargin$B$K$h$jM^@)$5$l$?!#(B3) 2meS-ATP$B$OFbHi:YK&AX$rF)2a$9$k(BFD-4$BNL$rM-0U$KA}2C$5$;$k$H$H$b$K!$$3$NA}2C:nMQ$O(BPPADS$B$K$h$C$FM^@)$5$l$?!#(B4) $B%i%C%HHxIt^uN.I8K\$K$*$$$F$bF1MM$K!$(B2meS-ATP$B$OHxItI=AX$KF)2a$9$k(BFD-4$BNL$rM-0U$KA}2C$5$;$?!#$^$?$3$NA}2C:nMQ$O(BPPADS$B$K$h$C$FM^@)$5$l$?!#(B

$B!!!Z9M;!![7l4IFbHi:YK&$K$*$$$F!$(BATP$B$O@8M}E*>r7o2<$K$*$$$F$b:YK&LL@QD4@a:nMQ$r<($7!$$=$N:nMQ$K$O(BP2Y$B2+]i$B$N>e>:$,4XM?$7$F$$$k$3$H!$$5$i$K$3$N$h$&$J:YK&LL@Q8:>/:nMQ$O!$FbHi:YK&AX$K$*$1$kJ*

$B!!(B(1) Clin. Exp. Pharmacol. Physiol. 28, 799-803, 2001.

$B!!(B(2) Life Sci. 72 1445-1453, 2003

 

$B!J(BP3$B!K(BPC12 $B:YK&$N(B ATP $B;:@8G=$K5Z$\$9%"%G%K%k;@%7%/%i!<%<$N(BP-$B%5%$%HAK32:^$N1F6A(B

$B!!F#?9W"9,!$K'@8=(8w!J@]FnBg3X!!Lt3XIt!!1R@8J,@O2=3X8&5f<

$B!!:YK&30$N(Badenine$B2=9gJ*$N@8M}E*0U5A2rL@$N0lC<$H$7$F!$%i%C%H3l?':YK&

$B!!(BLocke's$B1U$KMO$+$7$?(BDDA$BEy$N2=9gJ*$r(BPC12$B:YK&$K2C$(!$0lDj;~4V8e!$:YK&Fb$N;@2DMO@-J*

$B!!(BPC12$B:YK&$K(BdeoxyAdo$B$"$k$$$O(BDDA$B$r2C$($k$H!$:YK&Fb$N(BATP$B4^NL$OM-0U$KA}2C$7$?!#l9g$h$jA}2C$7$?!#(BP-$B%5%$%HAK32:^$G$O$J$$(BMethylAdo$B$r:YK&$K2C$($F$b!$$3$NMM$J1F6A$OG'$a$i$l$J$+$C$?!#0J>e$N7k2L$h$j!$(BdeoxyAdo$B$H(BDDA$B$O(BAdo$B$N(Bsalvage$B7O0J30$N(Bpathway$B$r2p$7$F(BPC12$B:YK&$N:YK&Fb(BATP$B4^NL$K1F6A$r5Z$\$9$3$H$,<(:6$5$l$?!#(B

 

$B!J(BP4$B!K(BP2Y12$B $B%1%b%?%-%7%9$H%$%s%F%0%j%s&B(B1$B=8@Q(B

$B!!B?ED70(B1$B!$>.@t=$0l(B1$B!$0f>eOB=((B2, 3$B!J9qN)1R8&!&(B1$BLtM}!$(B2$BBe3$B6eBg!&1!!&J,;R@)8f!K(B

$B!ZL\E*![%_%/%m%0%j%"$OCf?u?@7P7O$KFC2=$7$?LH1VC4Ev:YK&$H$7$FCN$i$l!$$=$N?@7PJ]8n:nMQ$H2a>j$J3h@-2=$K$h$k?@7P%@%a!<%8$NFsLL@-$,CmL\$rMa$S$F$$$k!#6aG/!$(BATP$B$H(BADP$B$,(BGi/o-coupled P2Y$BuBV$H4X$o$C$F$$$k!#:#2s2f!9$O!$(BADP$B$K$h$jM6F3$5$l$k%1%b%?%-%7%9$r2r@O$7!$%$%s%F%0%j%s&B(B1$B$N4XM?5Z$S$=$ND4@a5!=x$rD4$Y$?!#(B

$B!ZJ}K!![%_%/%m%0%j%":YK&$O@88e(B1-2$BF|$N?7@8;F%i%C%HBgG>$+$iD4@0$7!$(BDMEM 10% FCS medium$B$G(B1$B=54VG]M\$7$?$b$N$r;H$C$?!#%1%b%?%-%7%9e$K%_%/%m%0%j%"$r@\Ce$5$;!$(BDunn chemotaxis chamber$B$rMQ$$$FB,Dj$7$?!#%$%s%F%0%j%s$NJ,I[JQ2=$d%a%s%V%l%s!&%i%C%U%j%s%07A@.$OLH1V@w?'K!$rMQ$$$?!#(B

$B!Z7k2L$H9M;!![(BADP$B$K$h$jM6F3$5$l$k%1%b%?%-%7%9$O!$(BP2Y12$BFC0[E*AK32:^(BARC-69931$B$G>C<:$7$?$3$H$+$i!$@UG$e$K%_%/%m%0%j%"$rGEe$N%$%s%F%0%j%s&B(B1$B$,=8@Q$9$k$3$H!$$^$?$=$l$,%a%s%V%l%s!&%i%C%U%j%s%0$H(Bcolocalize$B$9$k;v$r8+=P$7$?!#(BADP$B;I7c$K$h$k%$%s%F%0%j%s$N=8@Q5Z$S%1%b%?%-%7%9$O%_%/%m%0%j%"$r(Bforskolin$B$d(Bdibutyryl cyclic AMP$B=hCV$9$k$3$H$K$h$C$F>C<:$7$?!#$3$N%$%s%F%0%j%s=8@QM^@)$O!$(BPKA$BAK32:^$G$"$k(BKT-5720$B$K$h$j2sI|$7$?$3$H$+$i!$(BPKA$B$O(BADP$B$K$h$jM6F3$5$l$k%$%s%F%0%j%s&B(B1$B=8@Q$N(Bnegative regulator$B$G$"$k$3$H$,M=A[$5$l$k!#0J>e!$(BADP$B$K$h$k%1%b%?%-%7%9H/8=$K$O!$%i%C%U%j%s%0$H(Bcolocalize$B$9$k%$%s%F%0%j%s&B(B1$B$N=8@Q$,I,MW$G$"$j!$$3$l$O(BcAMP/PKA$B0MB8E*$JM^@)@-@)8f$r

 

$B!J(BP5$B!K%_%/%m%0%j%"$K$*$1$k&A(B7$B%K%3%A%s@-%"%;%A%k%3%j%s7$B

$B!!NkLZCR5W(B1$B!$>>86L@Be(B1$B!$>>NS90L@(B2$B!$2$B!$=(!!OB@t(B1$B!$CgED5A7<(B1
$B!J9-Bg!&0e;uLtAm9g!!(B1$BLt8z2r@O!$(B2$B?@7P!&@:?@LtM}!K(B

$B!!;dC#$O$3$l$^$GK\8&5f2q$K$*$$$F!$%_%/%m%0%j%"$N(BP2X7$B%_%/%m%0%j%"=iBeG]M\:YK&$K$*$1$k&A(B7$B7$B2+$BF)2a@-$N9b$$%$%*%s%A%c%M%k$G$"$k$3$H$,CN$i$l$F$$$k$,!$%_%/%m%0%j%"$K$*$$$F%K%3%A%s(B(1 mM)$B$O0l2a@-$N:YK&Fb(BCa2+$B>e>:$r0z$-5/$3$7!$$=$N:nMQ$O&A(B7$B7$B$C$F!$&A(B7$B7$B

$B!!0J>e$N7k2L$h$j!$&A(B7$B%K%3%A%s@-%"%;%A%k%3%j%s7$B$l@5$*$h$SIi$K=$>~$9$k$3$H$K$h$j!$G>FbLH1V$r@)8f$9$k2DG=@-$,L@$i$+$H$J$C$?!#(B

 

$B!J(BP6$B!K(BP2X7$B

$B!!7nK\8w=S!$86ED6Q!$8^==N$>4!$9bLZK.L@!J@E2,8)N)Bg!&Lt!K(B

$B!ZL\E*![(BP2X7$B\:Y$OL$$@L@3N$G$J$$!#:#2s!$(BP2X7 cDNA$B$r%K%o%H%j(BB$B:YK&M3Mh(BDT40$B3t$KF3F~$7$FF@$i$l$?JQ0[3t!J(BDT40/P2X7$B:YK&!K$r:n@.$7!$:YK&;`M6F35!9=$K$D$$$F2r@O$7$?!#(B

$B!ZJ}K!![:YK&>c32@-$OBe2+$BG;EYJQ2=$OFC0[E*7V8w;X<(Lt(Bfura-2$B$rMQ$$$FB,Dj$7$?!#>.9&$N7A@.$O(BHoechst33258$B$N:YK&Fb$X$N

$B!Z7k2L$*$h$S9M;!![(BDT40/P2X7$B:YK&$K$*$$$F(BP2X7$B2+$BN.F~!$>.9&$N7A@.$J$i$S$K:YK&;`$NM6F3$,4Q;!$5$l!$(BDT40/P2X7$B:YK&$,5!G=E*$J(BP2X7$Be$h$j!$(BP2X7$B

$B!!$5$i$K!$:YK&<~4|$NJQ2=$K$D$$$F8!F$$7$?7k2L!$(BBzATP$B;I7c8e(B3$B;~4V$G(BG1/G0$B4|$N:YK&$N8:>/$,G'$a$i$l$?!#F1;~$K(BLDH$B$NJ|=P$bG'$a$i$l$?$3$H$+$i!$(BG1/G0$B4|$N:YK&$N8:>/$O:YK&;`$KM3Mh$9$k$b$N$H9M$($i$l$?!#$3$N$3$H$+$i!$(BP2X7$B

 

$B!J(BP7$B!K8IB+3K%7%J%W%9A0(BP2X$B

$BHKIZ1Q<#!$2CF#AmIW(B
$B!JEl5~;|7C2q0e2JBg3X!&Am9g0e2J3X8&5f%;%s%?!

$B!!%7%J%W%9EAC#$N4p442aDx$O!$<4:w=*Kv$NC&J,6K$,:YK&Fb(BCa$B%7%0%J%k$KJQ49$5$l$F@8$8$k%7%J%W%9>.K&$N3+8}J|=P$G$"$k!#0lHL$K3hF0EE0L"*<4:w=*Kv(BCa$B%7%0%J%kJQ49$rC4$&J,;R$OEE0L0MB8@-(BCa$B%A%c%M%k(B(VDCC) $B$G$"$k!#(BP2X$B2+$BF)2a@-$N$?$a!$(BVDCC$B$N4XM?$J$/%7%J%W%9$G$N3+8}J|=P$rM6H/$7$&$k;v!&@T?q$K$*$1$k(BP2X$B

$B!!MD.6=J3@-%7%J%W%98eEEN.(Bminiature EPSC (mEPSC) $B$O!$!A(B10 pA$B$N?6I}$r;}$A!$KhICLs(B5-10$B2sH/@8$9$k(B(basal mini) $B!#(BP2X$B2+$BB8:_2<$K$*$$$F$b:YK&30(BCa2+$B0MB8@-$K(BmEPSC$BIQEY$rA}2C$9$k;v@\EjM?$K$h$k%7%J%W%98e(BAMPA$B.6=J3@-%7%J%W%98eEE0L$r2+$BG;EY>e>:$O!$:YK&30(BCa2+$BHs0MB8E*<+H/%0%k%?%_%s;@J|=P$H$O0[$J$k5!9=$K$h$C$F(BCa2+$B0MB8E*%0%k%?%_%s;@J|=P$r9b8zN($Ge>:$,!$5a?4@-6=J3@-%7%J%W%9F~NO$NA}2C$HEy2A$G$"$k$H$$$&2DG=@-$r<($7$F$$$k!#(B

 

$B!J(BP8$B!K%7%J%W%9A0%"%G%N%7%s $B8IB+3K%7%J%W%9EAC#C;4|2DA:@-$N=$>~(B

$B!!DE;aE5;R!$HKIZ1Q<#!$2CF#AmIW!J;|7C0eBg!!?@7P@8M}!K(B

$B!!F0L.7l05!$7l1U%,%9J,05!$GY?-D%!$>C2=4I?-E8$J$I$N@8BNFb4D6-$K4X$9$kFbB!463P>pJs$O!$Bh(BIX,X$BG>?@7P$r7P$F1d?q8IB+3K$KEj1$B

$B!!8IB+$+$i8IB+3K%K%e!<%m%s$X$N%7%J%W%9EAC#$NC;4|2DA:@-$K5Z$\$9(Badenosine$B$N1F6A$H$=$N5!9=$N2rL@$rL\E*$H$7$F!$MD444'>uCG%9%i%$%9$+$i%[!<%k%;%k%Q%C%A%/%i%s%WK!$G6=J3@-%7%J%W%98eEEN.(B(eEPSC) $B$rLtM}3XE*$KC1N%5-O?$7$?!#8IB+$NO"B3;I7c(B(50 Hz, 2-10$B2s(B)$B;~$K4Q;!$5$l$kM6H/(BeEPSC$B?6I}$K$*$h$\$9(Badenosine$B$N1F6A$r8!F$$7$?!#8IB+O"B3;I7c;~$N(B1$B2sL\$H(B2$B2sL\$N(BeEPSC$B?6I}Hf(B(paired-pulse ratio, PPR) $B$O!$A45-O?%K%e!<%m%s$K$*$$$F(B1$B$h$jDcCM$G$"$j!$CxL@$JC;4|M^@)$r<($7$?!#(BAdenosine (100 ìM) $B$O!$(BPPR$B$r(B0.33$B!^(B0.04$B$+$i(B0.48$B!^(B0.05$B$KM-0U$KA}2C$5$;$?(B(n=35) $B!#:YK&30(BCa2+$BG;EY$r(B2 mM$B$+$i(B0.5 mM$B$KDc2<$5$;$k$H!$(BPPR$B$OM-0U$KA}2C$7$`$7$mC;4|A}6/$,8+$i$l$?!#$3$N;~!$(Badenosine$B$K$h$k(BPPR$BA}2C:nMQ$O4Q;!$5$l$J$/$J$C$?!#0lJ}!$(B20ms$B4V3V$GM?$($?O"B3;I7c(B(5-10$B2s(B) $BCf$N(BeEPSC$B?6I}$N;X?t4X?tE*8:?j$O(Badenosine$B$K$h$C$FM-0U$KCY1d$7$?!J;~Dj?t!'EjM?A0(B1.4$B!^(B0.5$B2s!$EjM?Cf(B1.9$B!^(B0.7$B2s(B; n=28$B!K!#$3$N$H$-!$(Badenosine$B$O!$8IB+O"B3;I7c$NBh0l;I7c$K$h$k(BeEPSC$B?6I}$r(B72.3$B!^(B2.7%q (n=46) $B$^$G8:>/$5$;$?$,!$BhFs;I7c$K$h$k(BeEPSC$B?6I}$K$OM-0U$J1F6A$r5Z$\$5$:(B(113.7$B!^(B12.4%; n=45) $B!$Bh;0;I7c$K$h$k$=$l$rA}Bg$5$;$?(B(175.5$B!^(B25.9%; n=30) $B!#$3$l$i$N(Badenosine$B$N:nMQ$O(BA1$BC<:$7$?!#(BAdenosine$B$O<+H/(BEPSC$B$N?6I}$*$h$SIQEY$K$O1F6A$r5Z$\$5$J$+$C$?!#(B

$B!!0J>e$+$i!$8IB+=*Kv%7%J%W%9A0(Badenosine A1$B2+$BN.F~$rM^@)$7!$%7%J%W%9EAC#8zN($N5^B.$J8:?j$r4KOB$7$F%7%J%W%98e1~Ez$rJ?C32=$5$;$k$3$H$K$h$j!$FbB!

 

$B!J(BP9$B!K%i%C%H4'=[4D$K$*$1$k%"%G%K%s%L%/%l%*%A%IBe $B$3$l$K$*$h$\$95u7l$N1F6A(B

$B!!:4F#70(B$B#1(B$B!$>>2,8y(B$B#2(B$B!$LZB<=c;R(B$B#2(B$B!JJ!Eg0eBg!&0e!&(B$B#1(B$BKc?l2J!$(B$B#2(B$BLtM}!K(B

$B!!(BATP$B$N5^@-EjM?$OH/:n@->e<<@-IQGo$rDd;_$5$;$k$3$H$,CN$i$l$F$$$k!#$3$N(BATP$B$N:nMQ$K$O(Becto-nucleotidase$B$,=EMW$JLr3d$r2L$?$7!$BNFb$GB.$d$+$K%"%G%N%7%s$KJQ49$5$l8z2L$r8=$9$H9M$($i$l$F$$$k!#0lJ}!$?46Z$N5u7l:F^uN.>c32;~$K$O(Becto-nucleotidase$B3h@-$NJQ2=$,<(:6$5$l$F$$$k$,>\:Y$OL@$i$+$G$J$$!#K\8&5f$G$O4'=[4D$K$*$1$k%L%/%l%*%A%I$NBe

$B!ZJ}K!![2, 5% CO2) $B$GK0OB$7(B37$B!n$K2C29$7$?(BKrebs-Ringer$B1U$rMQ$$$F(BLangendorff$BJ}<0$G(B4-5㎖/$BJ,$N^uN.$r9T$C$?!#^uN.$r3+;O$7$F$+$i(B20$BJ,4VJ?9U2=$5$;$?8e!$(B5$BJ,4V3V$K!$(BATP$B!$(BADP$B!$(BAMP$B!$%"%G%N%7%s$*$h$S3F%"%G%K%s2=9gJ*$N%(%F%N2=M6F3BN$r^uN.1UCf$KEjM?$7$?!#EjM?D>8e$K?4B!$+$iE)2<$9$k^uN.1U$r2s<}$7!$^uN.1UCf$NBeA0!$:F^uN.D>8e$J$i$S$K

$B!Z7k2L!&9M;!![@5>o?4$G$O!$(BATP$B!$(BADP$B$OB.$d$+$K!$(BAMP, $B%"%G%N%7%s$K$^$GBee$N7k2L$+$i!$4'7l4I>2$N(BATP$BJ,2r$K$O8e$N:F^uN.1UCf$K$O(BATP, AMP, $B%"%G%N%7%s$NBee$N7k2L$+$i!$5u7l5^@-4|$N4'7l4I>2$G$O(BCD39$B$H%"%G%N%7%s%G%"%_%J!<%<$,7l1UCf$KM7N%(B-$B>C<:$7!$(BATP$BBe/$7$F$$$k2DG=@-$,<(:6$5$l$?!#(B

 

$B!J(BP10$B!K%"%9%H%m%5%$%H$+$i$N<+H/E*(BATP$B$K$h$k:YK&Fb%7%0%J%kD4@a(B

$B!!>.@t=$0l(B1$B!$5\C]??M3H~(B2$B!$F#2<2CBe;R(B3$B!$0f>eOB=((B3,4
$B!J9qN)1R8&!&(B1$BLtM}!$(B3$BBe2$B@1Lt2JBg3X!$(B4$B6e=#Bg!&1!!&J,;R@)8f!K(B

$B!!%"%9%H%m%5%$%H$O$[$H$s$I$9$Y$F$N?@7PEAC#J*2+$B$,M7N%$5$l$k$3$H$ONI$/CN$i$l$F$$$k$,!$(BGi$B6&Lr7?l9g$N(BCa2+$B1~Ez$K4X$7$F$OJs9p$N0l4S@-$,L5$/!$ITL@$JE@$,B?$$!#(BDopamine$B$GG]M\%i%C%H3$GO%"%9%H%m%5%$%H$r;I7c$9$k$H!$(BGi$B6&Lr7?(Bdopamine D2$B2+$BG;EY(B([Ca2+]i) $B$,>e>:$7$?!#$3$l$O!$(BG$BCAGr2+$B1~Ez$O!$(BD2$B@\%j%s%/$5$;$k$H!$DcMFNL(Bdopamine$B$K1~Ez$9$k$h$&$K$J$C$?!#(BP2$B2+]i$B>e>:$r>C<:$5$;$?!#%"%9%H%m%5%$%H$O!$<+H/E*$K(BATP$B$rJ|=P$7$F$*$j!$$3$l$O(Bdopamine$B;I7c$K$h$jJQ2=$7$J$+$C$?!#0J>e!$<+H/E*$J(BATP$BJ|=P$H91>oE*$J(BP2Y1$B2+$B1~Ez$KI,?\$G$"$k$3$H!$$^$?%"%9%H%m%5%$%H$O(BATP$BJ|=P$rD4@a$9$k$3$H$K$h$j!$<+?H$N(BGi$B6&Lr7?2+$B1~Ez$r@)8f$7$F$$$k2DG=@-$,<(:6$5$l$?!#(B

 


$B$3$N%Z!<%8$N@hF,$X(B$BG/JsL\<!$XLa$k(B$B@8M}8&%[!<%`%Z!<%8$X(B
Copyright(C) 2004 National Institute for Physiological Sciences