Caffeine down-regulates β adrenoreceptors in rat forebrain

w s ~s~:~heiaa~r~cs sf ~.s~ae ~ a ~ r a ~ (s~ rag/~s rot 3 dsses)on ~a~echo~ami~e:~i~,a~ioa as,d hi,SirraSia fema~ ~ s : CaSfeineeahaaced ~he red~¢~ioai~ forebrain norep~nephrise }evigs.fo~towir4u-melhy~w-tyrosi~esitho~at aReri~gthe re-duct~on~ndoDaminelevels. Caffei~e reduce.~ ~gcg~s: i@:~fo~ebr~ia~ measured by ~he g ~ for |!H]d~hy@oalprenok~

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r~p~-tiVe~y; ~ere:~tedi ~me:da~:~hOw' ~E/atcaffeine seiectivdy ir~crdasesthe r~,te of norepinephrine afi~i~tio~ i~.m~ro,~ra~ and ~ga~~i~ ~ a~,s~cia~ with ~ smaHi~ significant rCd~ctionin# receptor d~rt~Ryin {h~:br~n area~ .....

~oterance d e v d o p s m many of ~,he acute hcm~y~ic effects o f caHei~¢in m a n [t IL The mecha~lism f '" uot ap~t@~at from ,these ~4~dies. Since caffeit~e s~im,ta~es bo~h higher cortical i:un~io~.s ~gsym~a~h¢~i¢ o u g l o w , the cetera1 nervous sysCem appears to E:e a like!y ta~g¢~ fo~ c a f f d n e ac~mn and a po~entiaI ait.¢ for caffeine tolerances.. F~.~r~ae~rnore, outfi.ow a~d

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selective radio|igands was used to determi~e de~.~ikv ( B ~ ) and.: of:~>:, a~. and 3 :drene~gic recep:ors [g], A]] ligartcg wer~.~ from New Eng)aad N ~ l e a r . [:H]Prazo',~in (17. ! el/retool)~a~ receptors), ~H!¢Io :{22~2-avA'~.8 C i / (az receptors} aa~ t: nt~Iol used, A::: assay~ were doae ~n f~r~a::ac~b~ approximate:y 0,5 mg m e m b r a : e prOte:a/mio L~gand co:¢eatrat::o:::: ;~,ere~ FH]praacrsm," ' ¢.i.~.~5--0.6 ~ " riM; [~H]do~tdine. ( L & 3 riM;-a~d :[~"H}:DHA; . . . . 0 . ~ - 2 ~M, bkm-spec:f~c bir~d~ng w~'as dete,m:ae8 in t~c >re.m~:ce of a¢:ore~i:'~eN~:~{~e c,:~nce:tr:~,ioaa wh~c~ bad prev:ousIy bee:~ shovm :,~ io~ ~,~:~e~ vo ma×imatiy i~hibi{ b : n d ~ g of t h ~ ~:gartd~ (tO" ~ M fc~ cloa~d{ne a~d l 0 - e M fm °

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TABLE ~NFLUENCE OF CAFFZqNE ON ADRENERG~C RE-Ci6PTOR ~{~ND~NG ~N R A i FOREBRA~N

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No change in affi~fi~:y(i.e. K~) for this aa~go~st ~i~ad wa~ ob~er~,~, i~ ¢~n~.:asL neither D,~,~ nor ~ of ~:)rebrain b ndmg of [~Hip~az.o~in c r [~H]c~0Ndh).e w:~ altered. Since ~is~ue levels of caffeiae ceuld d i r ~ ! y interfere w~th ra~:~igaad bmd~ug, ~e

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TN~ work wassupported by USPHS Gr~nt GM ~5431. Dr. Goldberg is Clinical A~sociated P-hy~i¢ian, Elliot V. N~'man C~iniea! Research Center, VanderbiIt Medical, School. I Be.~kowilz, B.A. a~d S~eetor~ S., The effect of c~ffe~t~eand theephy~ffne e~ ~he disposition of brai~ ~ e r o t o ~ N t~e raq Europ. J. Pharm~co1,~ 16 U97I) 322o~325. 2 Berkowi~z~ BOA., Specter, S. a~d Pe~.L W.~ T~e ingeracuon of caffe~ae, lheophytline and ~heobromine with ~og~o~raine oMda~e :~'~hibitor% ~ ;~r~p. ft. PbarmaeMo, i5 (!97t} 3~.5--32~ ? BerkoM~z, B . A . Tarver, J.H. and S~¢to:° S.~ Release ~f ~orepmepbri~e ie ~ e eemral nervous ~yg~em by th~ghyll{~e aed e~fffeir~e. E~mo~. ~o PharrnacoLo ~0 (~970) 64~.7t. 4 Corrodi. H.~ Fu×e, g , and Jons~.~a, G.. Effec:~ of caffeine on ce~trM monoamiae r~eurm~:. ~, Pi~n.~ Ann. ROVe Phar~acoL

h~oroFheny~a~nv:ne o~t arma¢o~ogi~° 28 (t973} ~o~ adenosine? Trend,~ t)if~ren~ia~ cam~';Jfien

m d-arnp~ammeo an~ ;ha~d D.G. and Oa~:c~, ~¢~ ~J~ bN~od pr,sssure~ N~w Engt