EU"opean Opioid Conference 2011, Krak6w, Poland Poster presentations

PS 111- 3 The possible role of endomorphin 2 biosynthesis and CART peptide in the nociceptive information processing in rat spinal dorsal horn: pharmacology and immunohistochemistry

Kornel Kiraly 1, Mark Kozsurek2, Zita Puskar2, Apolka Szentirmay 1, Csaba Fekete3, Andras Z. R6nai 1

1 Department of Pharmacology and Pharmacotherapy. Semmelweis University. Budapest Hungary; 2Dept of Anathomy. Hystology and Embriology. Semmelweis University. Budapest Hungary; 31nstitute of Experimental Medicine of The Hungarian Academy of Sciences. Budapest. Hungary

Background and Aim: While demonstrating the pos• Results: Inrathecally injected rCART(55-76) peptide, sibility of de novo biosynthesis of endomorphin 2 in which carries the N-terrninal He-Pro-He motif, exerted en• rat isolated L4,5 dorsal root ganglia from Tyr-Pro pre• domorphin 2- and opioid receptor-mediated antihyperal• cursor in the presence of DPP4 inhibitor He-Pro-He, gesic effect. Using quadruple immunostaing in transverse besides the heretic idea itself, two further features had sections of rat spinal cord at L4,5 level followed by con• to be considered. First, the biosynthesis took place at focal microscopy, we have shown in laminae 1-110 the the external surface of plasma membrane. Second, neural co-localization of endomorphin 2, CART and sub• while Tyr-Pro had to be provided exogenously, the stance P (possible Phe-Phe-Gly source) and contacts by other co-substrate must have been generated endoge• NPY-containing profiles (possible Tyr-Pro source). Fur• nously. Since similar endomorphin biosynthetic rnles thermore increased plasma membrane apposition with operate in rat spinal dorsal horn in carrageenan induced scattered intracellular staining of endomorphin 2 was inflammation, we investigated these aspects as well. found by electron microscopy in sections from plantarly Methods: Carrageenan-induced hyperalgesia was carrageenan-, intrathecally He-Pro-He-treated rats. studied in male Wistar rats. Drugs were given mainly Conclusions: These morphological findings do not intrathecally, occasionally subcutaneously. Morpho• prove either that endomorphin 2 biosynthesis takes logically multiple immunostaining was combined place the way we have proposed, or it happens at the with confocal microscopy or silver-intensified immu• external plasma membrane surface, they are at least nogold staining combined with electron microscopy. suggestive for these possibilities.

PS 111- 4 Dose-dependent potentiation by the 8 antagonist cha-TIPPpsi on the spinal antinociceptive effect of the J.l agonist DAMGO in opioid-naive rats

Apolka K. Szentirmay, Kornel P. Kiraly, Mahmoud AI-Khrasani, Erzsebet Lack6, Tamas Friedmann, Susanna Gyarmati, Julia Timar, Susanna FOrst, Pal Riba

Department of Pharamacology and Pharmacotherapy. Semmelweis University. Budapest. Hungary

Background and Aim: The role of 8 opioid receptors onist TIPPpsi eliminated the tolerance to the intrathe• in analgesia and the development of opioid tolerance cal (it) analgesic (tail-flick) action of the selective fl is not clear. We reported that the selective 8-antag- agonist DAMGO in mice and rats. This potentiating

Pharmacological Reports, 2011, 63, 226-264 241