The discovery of the important role of vagal nerves in control of gastric and pancreatic secretion by IP Pavlov in 1890

Transcription

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he discovery of the important role of vagal nerves in control of gastric and pancreatic secretion by IP Pavlov in 1890 The discovery of secretin as hormonal stimulant of pancreatic secretion by Bayliss and Starling in 1902; The discovery of gastrin as postprandial HCl stimulant by J.S. Edkins in 1906 The discovery that histamine is direct HCl secretagogue by L. Popielski in 1916 Synthesis of H 2 -receptor antagonists by J. Black 1972 and proof that they inhibit HCl stimulated by varierious stimuli (histamine, vagal excitation & meal) by Grossman and Konturek (1973).EC = HDEIJ HE?= BECKHAIE JDA@EI? LAHO B AKH D H = HACK =JE F=?HA=JE?IA?HAJE

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10 ' Brain stem Vagal efferent nerves Systemic circulation Secretin Cholecystokinin Vagal afferent nerves Fluids and electrolytes Enzymes NA, NPY Ach, VIP, GRP, I-cell S-cell? Entero-pancreatic reflexes Modyfikacja Hansena JT & Koeppena BM, 2002 Long vago-vagal reflexes.ec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

11 '! ++ HA ++ EIIJHK?JKH= OHA C=IJHE =IEJI+ JAH E = = E =?E@I=HA E@A JE?= J JD IAE C=IJHE IALAH= A?K =HB H IIK?D=I&++ #"= E =?E@B H I 6DA IJHK?JKH= BA=JKHAJD=J@AJAH E AIMDAJDAH=FAFJE@A>AD=LAI E AC=IJHE IJE K =JAIC=IJHE?=?E@IA?HAJE H++ IJE K =JAIC= > =@@AH? JH=?JE F=?HA=JE?A O AIA?HAJE EIJDA?=JE BJDAJOH IO HAIE@KA 1 FAFJE@AI MEJDC=IJHE E A=?JELEJO JDAJOH IO HAIE@KAEIE F IEJE $BH + JAH E KI MDE AE ++ E AFAFJE@AIJOH IO HAIE@KAEIE F IEJE %BH JDA+ JAH E KI 5K B=JE BJDAJOH IO E JDAC=IJHE FAFJE@A@ AI J=BBA?JEJIF JA?OC=IJHE 11 MDAHA=IJOH IO HAIE@KAE ++ EI= M=OIIK B=JA@J =E J=E JDA>E CE?= =?JELEJO 6DA E E = =?JELABH=C A JB HJDA++ F=JJAH B =?JELEJOEIJDA+ JAH E = DAFJ=FAFJE@A 7 E AC=IJHE JE= O J HA?AFJ HJAH A@++ HA?AFJ HI ++ E HA?AFJ HI?= A@ ++ HA?AFJ HI 6DA41) B++ B>? =@A BIFA?EBE? HA?AFJ HIB HC=IJHE CHA=J ODA FA@J A K?E@=JAJDAFDOIE CE?= =?JELEJO BJDAIAD H = FAFJE@AI KH1 IJEJKJAM=IE L LA@E A K?E@=JE BJDAHA B++ IAA.ECI# % 9AMAHABEHIJJ?= E AJDA=HA=E JDAI = > MA MDE?DHA A=IAI++ BH A1?A I" 7IE C++ 41) =IMA =IJDAIJE K =JE B F=?HA=JE?A O AIA?HAJE E DE>EJE BC=IJHE?IA?HAJE FJOE C > =@@AH? JH=?JE MAB EIFHA@ E = J OHA A=IA@E JDA BEHIJ#? BJDAKFFAHI = > MA E? K@E K A K K " "# 6DAIAABBA?JI CA KI++ MAHA? BEH A@KIE CAN CA KIFAFJE@A HA?AFJ H= J=C EIJI IK?D=I NEC K AFE A 9A = IJD=J++ D=IA JAH C=IJH A E A =?JELEJOJ E DE>EJC=IJHE?=?E@IA?HAJE " " C>AB HAL=C= AHLAID=@>AA FH F IA@J A@E=JAJDA>E CE?= ABBA?JI B++ >O MO= C"! MAID MA@JD=J JDAABBA?JI B++ E L LA?D E AHCE? AHLAI=IEJIABBA?JM=IIKFFHAIIA@>O =JH FE A"" "# 7IE CIFA?EBE?= J=C EIJI BHA?AFJ HIB H++ C=IJHE MAFH F IA@JD=J/42EI?=F=> A BHA A=IE C> JD++ IA?HAJ FDE?ABBA?JI BJDEIFAFJE@AI? EIDA@>OJDAFHAJHA=J A J MEJDIFA?EBE?/42 ++ = J=C EIJI"% "& *=IA@ JDAFHALA JE B++ ABBA?JI JDAF=?HA=IKIE C NEC K E@A AFE A MDE?D=HAIFA?EBE?= J=C EIJI B++ HA?AFJ HI MAFH F IA@ JD=JJDAIA= J=C EIJI? E JDAFHALA JE B=?KJAF=?HA=JEJEI H=JI>O LAHIJE K =JE MEJD?=AHK AE J=C EIJIMAHA B FH JA?JJDAF=?HA=JE?JEIIKA=C=E IJJDA@= AE 5E E =HFH JA?JELAABBA?JIMAHAHA? H@A@KIE CF=?HA=JE?F JAH E = DAN=FAFJE@A MDE?DMAHAID M FHALE KI OJ E DE>EJAN?HE A F=?HA=JE?IA?HAJE CI

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β E E@= O =AJDO = E HC= ANJH= JA 1 β 1= I =A?DJECA -HHACAH@AH 2 KAC)H?DCAI2DOIE ' %& " * =? 9,K?= 9),KH= J+ AJ=,ABE EJE J=C EI BDEIJ= E A0 HA?AFJ HI =JKHA '%!$ &# /H II = 1 JKHA 5 1 DE>EJE B=?E@IA?HAJE C>O AJE= E@A =DEIJ= E A = J=C EIJ=?JE C 0 HA?AFJ HI /=IJH A JAH CO '%" $$ #% #! 0EIJ= E 1 0EIJ= E A /9 IJAD A + H+A@I * IJ EJJ A*H M '#$ FF &' ' " /HAC HO4 6H=?O0 6DAFHAF=H=JE FAHJEAI BC=IJHE '#' "' % % # /HAC HO4) 6H=?O0 6DA? IJEJKJE FAHJEAI BJM C=IJHE IANJH=?JA@BH D C = JH= K? I= /KJ '$" #! # $ /HAC HO0 0=H@O2 AI,5AJ= 6DA= JH= D H AC=IJHE 5JHKJKHA BC=IJHE =JKHA '$" " '! '!! % JKHA 5 /H II = 1 )?E@HAIF IAJ C=IJHE =JA@FAFJE@AI /=IJH A JAH CO '$$ # $# $# & JKHA 5 /=IJHE E AFAFJ=FAFJE@A1 + 1 #! )F JA JC=IJHE?IJE K = JE = ),EC,EI '$% &# ' ' JKHA 5 = I 2A J=FAFJE@AE BKIE JAIJ /=IJH A JAH '$% % JKHA 5 9OI? E) A IO -BBA?J B A@E?= L=C J O C=IJHE?HAIF IA J CH=@A@@ IAI BFA J=C=IJHE E A /=IJH A JAH CO '$& #"!' " JKHA 5 +EAI MI E =M HA AJ= -BBA?JI BAFE@AH = CH MJDB=?J H C=IJH E JAIJE = IA?HAJE I ) 2DOIE '&" "$ /#& #&$,A >E I ME?, /HAC HO0AJ= 1 DE>EJE B=?E@B H =JE >OAFE@AH = CH MJDB=?J HE JDAEI =JA@H=>>EJC=IJHE?C '&$!%&!"% #%! JKHA 5,A >E I E) 9=H A?D= *H MI E6 /HAC HO0 4 A BAFE@AH = CH MJD B=?J HE DA= E C = K?AHIE H=JI /=IJH A JAH CO '&& '"!!% " JKHA 5 *EA = I E9 JKHA 9 A IO ;= = = E 4A BAFE@AH = CH MJDB=?J H C=IJHE?IA?HAJE E DK = I 5?= /=IJH A JAH '&' " "&# "' # JKHA 5 6D H2,A >E I E) H 4 + F=HEI BIA?HAJE =?JELAE JAIJE = FAFJE@A F=?HA=JE?IA?HAJE CI /=IJH A JAH CO '%# $& # % #!#

14 '$ $, I?D A5, I?D A9 4 I?D9 JKHA 5 9K I?D-,A E C *E?=H> E?) 2? JA J BFKHADK = F=?HA=JE? KE?AE HAIF IAJ CH=@A@@ IAI BIO JDAJE? IA?HAJE /=IJH A JAH CO '%$ % #!! #!$ % JKHA 5 2K?DAH) 4=@A? E6 + F=HEI BL=I =?JELAE JAIJE = E IJE K =JE BF=?HA=JE?IA?HAJE ## "'% #' & JKHA 5, I?D A5, I?D A9 9K I?D-,A E C + F=HEI BF=?HA=JE? HAIF IAIJ F HJ= E?IA?HAJE ) 2DOIE '%%! -#$ #& ', I?D A5, I?D A9 4 I?DAJ= 8=I =?JELAE JAIJE = FAFJE@A =IA?HAJE E AF=HJE= =C EIJB HF=?HA=JE?IA?HAJE E = /=IJH A JAH CO '%% %! "%& "&! JKHA 5,A >E I E) H 4 9K I?D- -BBA?JI B JE E IA?HAJE CI /=IJH A JAH '%$ IKFF!' #% $! JKHA 5 H 4,A >E I E 9K I?D- -BBA?J B JE E F=?HA=JE?IA?HAJE 2B KCAHI )H?D '%$!$") '%!! JKHA 5,A >E I E) H 4 9K I?D-,A E C -BBA?J B! A JE E C=IJHE? IA?HAJE IAHK C=IJHE ALA K? I= CI '%% $" $$# $%!! JKHA 5 6D H2 H 4,A >E I E) 5?D= O)8 1 B KA?A B AJDE E A A AFD= E HFDE A O A A?JHE?=?JELEJO BI = > MA ) 2DOIE '&!& /!&"!&'!" JKHA 5 6=I AH +EAI MI E + O,0 5?D= O)8 -BBA?J BCH MJDD H AHA A=IA E DE>EJE CD H A C=IJHE?IA?HAJE K? I= M C=IJHE /=IJH A JAH CO '%$ % %!% %"!# JKHA 5 6=I AH >JK ME? 9 + O,0 5?D= O)8 -BBA?J BCH MJDD H A HA A=IA E DE>EJE CD H A D H AIIJE K =JE CAN?HE AF=?HA=JE?IA?HAJE + E 1 LAIJ '%$ #& $!$, I?D A5, I?D A9 4 I?D9AJ= 1 DE>EJE >OI =J IJ=JE BIA?HAJE IJE K =JA F=?HA=JE?IA?HAJE E = =IJK@OMEJDFKHAF=?HA=JE? KE?A /=IJH A JAH '%% #' $!!% JKHA 5 5MEAH? A MEA?EA E - A IO 9EAH >E? E -BBA?J BI =J IJ=JE A= E = K?AHF=JEA JI ),EI,EI '%% '& '&&!& JKHA 5 6=I AH H 4,A >E I E) + O,0 5?D= O)8 -BBA?J BI =J IJ=JE = = CI 2H?5?-NF*E A@ '%% ## #' #!' 6D H2 H 4 JKHA 5 -BBA?J BI =J IJ=JE O A A?JHE?= =?JELEJO BI = > MA ) 2DOIE '%&!# - "' #" " JKHA 5 6=I AH *E I E,A C) = IA * = AHI 2DOIE CE?= H E =JE B?D A?OIJ E E HA CI ) 2DOIE '&$ # /!'!'% " JKHA 5 MEA?EA >JK ME? 9 FF* A IO 4 L=JE +D A?OIJ E E E JDA E DE>EJE BC=IJHE?IA?HAJE FJOE CE DK = I,ECAIJE '' "# & " JKHA 5 *E I E 6=I AH +EAI MI E 4 A B?D A?OIJ E E E JDAE DE>EJE B C=IJHE?IA?HAJE CI '' "# "%% "&' "! MO= C+ 2DOIE CE?= A?D= EI I B?D A?OIJ E E =?JE F=?HA=JE?IA?HAJE E H=JI ) 2DOIE ''$ % / % "" JKHA 5 6=I AH >JK ME? 9 -BBA?J B=JH FE IAIJ CA KI CA KI?D A?OIJ E E,EC,EI5?E'% % ' '% "# JKHA 5 JKHA 9 = AHI+* 6=I AH *E I E 4 A BIA?HAJE E JDA IJE K =JE BF=?HA=JE?IA?HAJE E? I?E KI@ CI -BBA?JI B=JH FE =J IJ=JE 1 J 2=?HA=J '&%!!# "$,A >E I E) JKHA 2+ JKHA 5 4 A BC=IJHE A?OIJ E E E JDACH MJD FH JEC=?JE B> = K? 4ACK =J HO 2AFJE@AI '' %!"!!#"

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