Leptin transiently antagonizes ghrelin and long-lastingly orexin in ...
Leptin transiently antagonizes ghrelin and long-lastingly orexin in ...
Leptin transiently antagonizes ghrelin and long-lastingly orexin in ...
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6350 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol November 7, 2008 Volume 14 Number 41A LY294002 50 mmol/L, 1 hGhrel<strong>in</strong> 10 -10 mol/LB LY294002 50 mmol/L, 1 hOrex<strong>in</strong> 10 -10 mol/LC Wortmann<strong>in</strong> 100 nmol/L, 1 hOrex<strong>in</strong> 10 -10 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L[Ca 2+ ]i (nmol/L)600400200[Ca 2+ ]i (nmol/L)600400200[Ca 2+ ]i (nmol/L)60040020000 20 40 60t /m<strong>in</strong>00 20 40 60t /m<strong>in</strong>00 20 40 60t /m<strong>in</strong>DMilr<strong>in</strong>one at 10 mmol/L, 30 m<strong>in</strong>EMilr<strong>in</strong>one at 10 mmol/L, 30 m<strong>in</strong>Ghrel<strong>in</strong> 10 -10 mol/LOrex<strong>in</strong> 10 -10 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L600600[Ca 2+ ]i (nmol/L)400200[Ca 2+ ]i (nmol/L)40020000 20 40 60t /m<strong>in</strong>00 20 40 60t /m<strong>in</strong>F U0126 10 mmol/L, 30 m<strong>in</strong> G STAT3 <strong>in</strong>hibitor peptide 500 mmol/L, 30 m<strong>in</strong>Orex<strong>in</strong> 10 -10 mol/LOrex<strong>in</strong> 10 -10 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L<strong>Lept<strong>in</strong></strong> 10 -12 mol/L600600[Ca 2+ ]i (nmol/L)400200[Ca 2+ ]i (nmol/L)40020000 20 40 60t /m<strong>in</strong>00 20 40 60t /m<strong>in</strong>HNeurons <strong>in</strong>hibitedby lept<strong>in</strong> (%)6040200Ghrel<strong>in</strong>12/20 7/12 6/10 6/10Orex<strong>in</strong>809/205/10 5/104/960Control2/12LY2940021/111/10Wortmann<strong>in</strong>Milr<strong>in</strong>one5/15U0126STAT3 <strong>in</strong>hibitorIAmplitude<strong>in</strong>hibition (%)402002020Control12a12LY29400211b1010a10Wortmann<strong>in</strong>Milr<strong>in</strong>oneGhrel<strong>in</strong>Orex<strong>in</strong>109 1015U0126STAT3 <strong>in</strong>hibitorFigure 2 <strong>Lept<strong>in</strong></strong> suppresses <strong>ghrel<strong>in</strong></strong>-<strong>in</strong>duced <strong>and</strong> <strong>orex<strong>in</strong></strong>-<strong>in</strong>duced [Ca 2+ ]i <strong>in</strong>creases via different signal<strong>in</strong>g pathways <strong>in</strong> NPY neurons. A-G: Effects of <strong>in</strong>hibitorsfor signal<strong>in</strong>g molecules on the lept<strong>in</strong> action aga<strong>in</strong>st <strong>ghrel<strong>in</strong></strong> <strong>and</strong> <strong>orex<strong>in</strong></strong>. Pre<strong>in</strong>cubation for 1 h with 50 mmol/L LY294002, an <strong>in</strong>hibitor for PI3-k<strong>in</strong>ase, <strong>in</strong>terfered with lept<strong>in</strong>action to suppress [Ca 2+ ]i responses to <strong>ghrel<strong>in</strong></strong> (A), but not <strong>orex<strong>in</strong></strong> (B). Pre<strong>in</strong>cubation for 1 h with 100 nmol/L wortmann<strong>in</strong>, another PI3-k<strong>in</strong>ase <strong>in</strong>hibitor, little affected thelept<strong>in</strong> suppression of <strong>orex<strong>in</strong></strong>-<strong>in</strong>duced [Ca 2+ ]i <strong>in</strong>creases (C). Pre<strong>in</strong>cubation for 30 m<strong>in</strong> with 10 mmol/L milr<strong>in</strong>one, a PDE3 <strong>in</strong>hibitor, blocked the lept<strong>in</strong> action to suppress[Ca 2+ ]i responses to <strong>ghrel<strong>in</strong></strong> (D), but not <strong>orex<strong>in</strong></strong> (E). Pre<strong>in</strong>cubation for 30 m<strong>in</strong> with 10 mmol/L U0126, an <strong>in</strong>hibitor for MAP-k<strong>in</strong>ase, little affected the lept<strong>in</strong> action tosuppress <strong>orex<strong>in</strong></strong>-<strong>in</strong>duced [Ca 2+ ]i <strong>in</strong>creases (F). Pre<strong>in</strong>cubation for 30 m<strong>in</strong> with a STAT3 <strong>in</strong>hibitor peptide at 500 mmol/L, did not significantly alter the lept<strong>in</strong> suppressionof <strong>orex<strong>in</strong></strong>-<strong>in</strong>duced [Ca 2+ ]i <strong>in</strong>creases (G). H: The number of neurons whose [Ca 2+ ]i responses to <strong>ghrel<strong>in</strong></strong> or <strong>orex<strong>in</strong></strong> were suppressed by lept<strong>in</strong> <strong>in</strong> the presence of <strong>in</strong>hibitorsis expressed by percentage. The numbers above the bars <strong>in</strong>dicate the number of neurons <strong>in</strong>hibited by lept<strong>in</strong> over that responded to <strong>ghrel<strong>in</strong></strong> or <strong>orex<strong>in</strong></strong>-A. I: Reduction ofamplitudes of [Ca 2+ ]i responses to <strong>ghrel<strong>in</strong></strong> or <strong>orex<strong>in</strong></strong>-A by lept<strong>in</strong> is expressed by percentage. a P < 0.05, b P < 0.01 vs control. The data regard<strong>in</strong>g <strong>ghrel<strong>in</strong></strong> <strong>in</strong> H <strong>and</strong> I were<strong>in</strong> part taken from our previous paper [17] .www.wjgnet.com