Peripheral cbolecystokininA and cbolecystokinino ...

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on gastric chief cells 7,. As far as the eNS is concerned. CCK-8-sulphalc. (CCK·8S). injected inlo the lateral cerebral ventricle of anaesthetized rats. induced Il ...
ITAL J GASTROf.r-'TEROI. HfJ'Al'OI.

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Peripheral cbolecystokininA and cbolecystokinino receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate C. Blandizzi. G. Lazzeri. O. Carignan i. R. Colucci. F. Baschie ra. M. Togncui. G. Placanica. M . Del Tacca

Baclcground. Peplitle.f vf clmlecysrokinin Jamily regllime I'llrimu plly.fiological Ilction,l' by (Icting til (l'1'1'I of celllmi lI('rW)U,I' sy,uelll, Aims. Tv: I ) itlwmigatt' p(J,f.I"iblt' injlllcna of ('t'lI/raJ clIO/C' cystokinin pm/m'aY,f on ga,flric pepsinogl~n am/ acid ,fcere· timu; 2/ dlllraCleri:e 1,lwnlw('%giclll l"vjile and lo(."ation of droil:c.I',ftok;IIill " ("t'ptor ,l"Ubt)"pe,~ i/ll'(){I'f'd i" gtl.ftric /ifJet",t I)J cemmUy UPI)lied c}w!t'(."Y,fwki"ill·8·.mlplrate (dwle' c)"slOkillill.8S ). Methods , U",tlu/IIe·otloe,I'II,ct;U!(1 rau werc ,flfbje('led 10 cm/limlOus pt!rfrl.~i(J/1 oj gllsrr;c lumen, "e,Min "~ Ft'I,f ill per· JII,~tlIe were detemlined b)' enzymmic (/.f,WI,\' l)Used 011 ,Ipee· lroplrotomt'lric nll!(JSIlrt:mem oj products gt'llermetl by pep· ric digestio" of b(JI'i"l' Iwemoglohin, Acidity II'"U mcu,fll rt'd by al/lUllimic potem;omelric lirrotion vf hydrogen ions, Results, Followin g itlfrtU'erebrol'emrit'lIlar injeclio n, cholec-y,v tokinill·8S itlcreased both pelJsinogen tlIId lIci(1 OIflJlUl, I" addiliol/, i1ltrtll'en(I/I,~ d JOle{'yswkillil/·8S sli"I!I' 1(llell pe/1Iic and (lcid .{ecreriolls more promptly ami at lo w· er doses Iltan after central illjecliOlI, Sti"",lallt effects of cellfrally applied f:lwlef:y,fwkinin·8S II'er(' nol affected by immt't!ll'brol"emriclllar injeclion of df'\·(I t.el'ide (cl/olecys· luki";",, receptor lIntllgonist) or L·365,26O (clwlecystokin· ill/l receptor antagonist) or by bilalera/l'agoromy. Hawel'f'r. illlr{n'f'lUmS de l'aupide partly anwgo"it.ed pep,figoglll! ac· tio" of immcerebrol'l'flrriclI/(l r dwlecystvkini,,·8S witllOlI/ "ffeeling its acid 1t)1,erl'et'n.'lOry effect, whcretls after intm· vellOllS injection of L · 365,260 peptic 1t.\1JerSecretiall t'I'oke(1 by imrocl'rebrollt!lllriCilia r clw lecystvkinin·8S II '(U partial· 1.1' prel'f'tlred and acid respo flu II'£U compleuJ)' blockell. Simi/fir effects wert' e;fer/ed by imral't'flOIIS del'{I:e/)ide find L ·365,260 (Igain.l" imrfll'elw /iS dw{ecyswki"i,,·8S, A com· pirIe blockade of pl'p,vigoglle effecu induced by intracere· bff)"elllriclliar or ;ntral 'eno/I,~ c1wiecysrol.:illill ·8S Wfl5 ob· lIIinetl after combiner! illlml'cntJII,V tremme'" with del'a:.epi· tit' "II/,t L ·365,26O. Gm-rric hyperSe('fetlH)' effecu of imra·

"·rm,.: Dil'isir". 'if PII(Ir",(/("()lng), /111(1 Clte"wlltt'rtJ/J)', DqHlrtllll'III of O"col, linle anemian has been paid to the possible influence exerted by central mcdialors on the regulution of gasu;c pepsinogcn secretion. Accordingly. the present study was de· signed in an attempt to pursue a dual purpose: a) to in· vestig:uc the possible infl uence exen ed by cc ntra l CCKe rgic pathways on basal pepsinogen and acid se· cretion in the anaesthetized rat model: b) to character· izc the phannacological profile and location of CCK receptor s ubtypes involved in the stimulant effects of cen trally applied CCK·8S.

spcx base. was carefu lly introduced through the ho le in the s kull to a depth o f 4 mrn, and fixed to the sku ll sur· face with screws and dental ce ment. Animals were al· lowed to recover from the operation for 3-6 days. Twe nty·four hours before the experi ments.: the animals were maintained in single cages. with wire-net bot· toms. and deprived of food . Access to water ad libiwm was allowed until one hour before the experiment. At the time of the experiment. the drugs under inves· ti gatio n were administered by intrace rebroventricul ar (icv) or intravenous ( iv) route. In the fomlcr case. drug solutions (2.5 Ill) followed by 2.5 ).ll of saline so· IUlio n ( 154 mM NnC!) were injec ted into the latera l ventricle of the brain by means of a 10 III Hamilton microsyringe con nected to the gu ide cannula by poly· ethy lene lUbing . The soluti ons were injected within 20 seconds. At the end o f the experime nts. the correct locatio n of the cannula in the lateral ventricle wa"i checked by injecting 10 J.11 of dye (0 . 1% to lu idine blue) . The visua li zation of dye on the walls of the lat· era l ve ntricle indicated the exact location of the icY injection. When using the iv route. the left femoral vcin was exposed and the drugs under investigation were injected within 20 seconds. dissolvcd in a 200 ).ll volume of vehicle solution.

Materials and Methods Animals tIIlll drug lIt/mi" istration procedures The expcri menL1

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