Effects of: Opioid and non-dpiotd peptides intrathecally administered on nociceptive transmission

S230 / 341 Poster SPINAL.W) SUPPA SPINALXI'IONSOF PRO-=PHALIN A Monday ON Ih'IESTINAL TRANSIT (GIT)AN3 URINARY tilacier 1 BLADDER MOTILITY (UBM). A.Dray*, F. Porreca, T.F. Burks,* Department of Pharmacology, Medical School, Universityof Arizona,Tuzson,AZ 85724,USA. Aim of Investigation:Little is known about the fimcticnof proenkephalinA de??-&-peptides in the CNS though they posses analgesicactivityard interact with several opioid receptorsubtypes-in vitro. Since analgesicsinhibitGIT at-dUBM centrallyby specificopioid receptoractivationwa have utilizedthese visceral systemsto elucidatethe physiologicalsignificance of several proenkephalinA frqnents. Me'chcds:GIT was measured in mice 35 minutes after an ora15%r marker and the central eiininistraticn of a peptide. Transitwas expressedas the geinetric center of radioactivity measured in segmentsof the excisedtil. A bl&ler catheter ard pressure transducerwere used to measure spontaneousisanatric bladder contractionsin the anesthetized rat. All peptidesw=re tiinisteredby intracerebroventricular (i.c.v.) or intrathecal(i.t.) microinjection. Results: All the proenkephalin% fra+qen$, PeptideE, BAM 22P, y 12P, metenkephalin(ME)metenkephalin-Arg-Gly-Leu(MFAGL), matenkephalin-Arg-Phe (MEAP) and Peptide F showed activity by inhibitingGI transit and rhythmic bladder contractions. In general these substances appeared more potent following i.t.than i.c.v.adhninistration. Also PaptideE an3 FW 22P were the most potent frqnants tested (l-20ug). BAM 12P arilPeptideF were less active (10-40Vg) and ME, MFAGL and MFAP ware the least active (100-400 ug). Conclusions:Thesedata supportthe involverentof centralopioidmechanisns in visceralcontroland that proenkephalin A fragmentshave aphysiologicalrole in this respect. The inhibition of GIT and UBM also suggest that these substancespossesmu-anddelta opioidactivity,-in vivo. -

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asure" also

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Conclusions: participate, spinal

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342 Poster Monday Glacier 2

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nociceptive

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