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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 BC=IJHE?= @ F=?HA=JE?IA?HAJE
JE B KA?A@>O>? E C?D E AHCE? AHLAIMEJD=JH FE A 6DAFDOIE CE?= H A BC=IJHE M=IGKAIJE A@ D MALAH @KAJ JDA@EI? LAHO>O2 EID FDOIE CEIJ 2 FEA I E B L LE '$>KJFK> EIDA@E ' JD=J DEIJ= E A >KJ JC=IJHE EI=@EHA?J= @F JA JIJE K = J B NO JE?C = @IJD=J @ AI J@AFA @KF L=C= AHLAIIA?JE HI? F = E A 6DEI@EI? LAHO HAFHAIA JI=@EIJE?J2 EIDJH=?AJD=JEIIJE HA? C E A@= @ALA HA?AELA@=IJH C? BEH =JE @KAJ @ALA F A J BJDAF JA J= J=C EIJI BDEIJ= E A0 HA?AFJ HIIK?D=I?E AJE@E A= @H= EJE@E A MDE?DD=LA>AA IK??AIIBK O =FF EA@E JDAJHA=J A J B=?E@ FAFIE @EI H@AHIE DK = I 9EJDJDA? E E?= KIA B0 HA?AFJ H= J=C EIJI JDAHAMAHA K AH KI2 EIDJH=?AIE JDABE @E CI >O/H II = = @ JKHA JD=JJDAIA= J=C EIJIIKFFHAIIC=IJHE?=?E@ IA?HAJE E @K?A@ J O>ODEIJ= E A>KJ= I >OC=IJHE = @ H@E =HO A= H ID= BAA@E C FH LE@E CAN?A A JIKFF HJB HJDA??AFJ BDEIJ= E AH=JDAH JD= C=IJHE =I=? BE =?DA IJE K =J H B NO JE??A I=IIKCCAIJA@>O +. + @A! 6DAB=?JJD=JJDAIA@HKCI=HADECD OABBA?JELAE JDAJHA=J A J B =?E@ FAFIE @EI H@AHIE @E?=JAIJDADEIJ= E AIJ HOD=IFH LE@A@=FH=?JE?= KIA B 0 >? AHIE DK = I -=H OFD=IA BC=IJH E JAIJE = A @?HE CO 6DA@EI? LAHO BIA?HAJE >O*=O EII= @5J=H E C%= @C=IJHE >O-@ E I & =H A@JDA>EHJD B= AMI?EA?A BA @?HE CO JDA = A HECE =JE C BH JDAJAH D H = BH /HAA 1AN?EJAFH F IA@>O9 0=H@OB H=?DA E?= AIIA CAH>OMDE?D A HC= ANAH?EIAI= E B KA?A = JDAH 6DA@ALA F A J BC=IJH E JAIJE = A @?HE COM K @ J>AF IIE> A MEJD KJ 6DAFDOIE CE?= E@A JEBE?=JE B K AH KI AMD H AIIK?D=I?D A?OIJ E E A JAH C=IJH A E?HAJE KH C=IJH A LE E E E @K?HE E 2H CHAIIE FAFJE@A>E?DA EIJHOE EJE=JA@>OJDAJA= I B4 /HAC HO= @ A AH B ELAHF 4ADBA @ B+ FA D=CA = @- HFAI= @8 KJJ B5J? D ;= =ED=H= B5DE K =E =F= = @! A=IKHA A J BJDAJE EAIJGK= JEJEAI BFAFJE@AD H AKIE CJA?D EGKA BH=@E E K =II=O41)>O5)*AHI = @4 ;= ME '#' 2KHEBE?=JE BC=IJHE = @C=IJHE?D A?OIJ E E B= E O BFAFJE@AI,AIFEJAJDA? JH LAHIOIKHH K @E CJDAC=IJHE DOF JDAIEI B-@ E I& JDAEI =JE B=DEIJ= E A BHAAC=IJHE FAFJE@AM=I=?DEALA@>O =H L'E *=> E I,AF=HJ A J B2DOIE CO=J?/E 7 ELAHIEJO B6 H J 4 /HAC HO = @DEI? => H=J H0 6H=?O" #MAHAIK??AIIBK E FKHEBE?=JE BC=IJHE MEJDJDADA F B=5AFD=@AN?DH =J CH=FDO 6DAIK>IJ=?A?D=H=?JAHE A@>O/ A AH=J ELAHF =IDAFJ=@A?=FAFJE@A " MAECDJM=IB K @J ANEIJ E JM B H I?= A@C=IJHE 1MEJD KJJOH IE AIK B=JE = @C=IJHE 11MEJD IK B=JE BJOH IE A 6DAIAC=IJHE FAFJE@AI >J=E A@BH F H?E A= JH= K? I= &$
&% MAHAI B K @J >A= IJE@A JE?= J DK = C=IJHE AN?AFJB HJDA IK>IJEJKJE B AK?E AB H AJDE E A=JF IEJE BELA" $ 1 =@@EJE J C=IJHE MEJD%= E =?E@I/ %= @!"= E@=JA@= @C O?E A ANJA @A@C=IJHE /!" =IMA =I =HCAH A?K =HC=IJHE FHA?KHI HIIK?D=IFH C=IJHE = @FHA FH C=IJHE D=LA>AA E@A JEBEA@E IA?HAJ HOCH= K AI BJDA/?A I= @= I E JDAC=IJHE = E CAH - EI IO @H A= @C=IJHE? H? HA?J= JK HI.EC 9DA JDAIJHK?JKHA BC=IJHE >A?= A M IALAH= CH KFI BHAIA=H?DAHI @ALA FA@C=IJHE 41)= @ANF HA@JDA>E?DA EIJHO= @FDOIE CO BJDEI D H A 9EJDJDA=@LA J B@EI? LAHO FKHEBE?=JE = @IO JDAIEI B = HCKJD H AI KH1 IJEJKJA B2DOIE CO@ALA FA@= E JAH =JE =? FAH=JE MEJD = H?A JAHI BD H = FAFJE@A>E?DA EIJHO= @IAHLA@=I= AL= K=JE?A JAH B >E CE?= =?JELEJO= @JDA A?D= EI BHA A=IA BJDAIAFAFJE@AI,KAJ? IA? => H=JE MEJD4 /HAC HO= @DEICH KF=JJDAFAFJE@A => H=J HO B1 FAHE= +DA E?= 1 @KIJHEAI 7 MA >J=E A@= @KIA@B HJDA BEHIJJE ADK = FA J=FAFJE@A1+1#! JDA?= A@FA J=C=IJHE E? K@E C JDA+ JAH E = IAGKA?A BC=IJHE / O 6HF AJ )IF 2DA 0 MDE?DID MA@ IE E =H=?JE C=IJHE?=?E@IA?HAJE =IC=IJHE EJIA B% 6DEIFAFJE@A M=IB K @J E @K?A =NE = C=IJHE?=?E@=J=@ IA B " C CIA?HAJE MDE?DEIIE E =HJ JD=J >J=E A@MEJDDEIJ= E A >KJLEHJK= O@AFHELA@ BJDA G-cell Pre-progastrin Progastrin Glycine-extended gastrin-34 and -17 Secretory granule Amidated gastrin-34 and -17 Gastrin Blood vessel Amidated gastrin-34 (G34)and -17 (G17) Gly-extended G34 (Gly-G34 &-17 (Gly-G17) Progastrin (ProG) Cell membrane HCl stimulants; G-17 & G-34 Trophic targets; G-17, G-34 Gly-Gly, Progastrin - Stomach, gastric cancer - Colon, colorectal cancer - Liver, hepatocellular cancer.ec /=IJHE EJI A?K =HB H IE?EH?K =JE = @JDAEHFHA?KHI HI=IF JA JIJE K = JI BC=IJHE? =?E@IA?HAJE CH MJDB=?J HB HC=IJH E JAIJE = K? I== @?=?AH?A I
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