4. B. Fjalland, A. V. Christensen, and I. Hyttel, Naunyn-Schmiederberg's Arch. Pharmacol., 301, 5 (1977). 5. T. Ljundberg and U. Ungersted, Psychopharmacology, 60, 303 (1979). 6. R. I. Miller and C. R. Hiley, Nature, 248, 596 (1974). 7. E. Richelson, Psychiat. Annu., I0, 21 (1980). 8. E. Richelson and A. Nelson, Eur. J. Pharmacol .... i03, 197 (1984). 9. P. Seeman, Pharmacol. Rev., 32, 229 (1980). i0. S. H. Snyder and H. I. Yamamura, Arch. Gen. Psychiat., 34, 236 (1977). ii. S. H. Snyder, D. Greenberg, and H. I. Yamamura, Arch. Gen. Psychiat., 31, 58 (1974). 12. H. I. Yamamura and S. H. Snyder, Proc. Natl. Acad. Sci. USA, 71, 1725 (1974). EFFECT OF THE HEXAPEPTIDE DALARGINON ORNITHINE DECARBOXYLASE ACTIVITY IN THE DUODENAL MUCOSA OF RATS WITH EXPERIMENTAL DUODENAL ULCER K. N. Yarygin, A. G. Shitin, V. M. Polonskii, and V. A. Vinogradov UDC 616.342-002.44-085.31:[547.95:547,943]-036. 8-07:616.342-008.931:577.152.213 KEY WORDS: ornithine decarboxylase; duodenal ulcer; dalargin; opioid peptides Previously the authors showed that several endogenous opioid peptides and their synthetic analogs have marked antiulcerative activity in rats with an experimental model of cysteamine- induced duodenal ulcer [i, 2]. The substance with the strongest antiulcerative potential was found to be a hexapeptide with the structure Tyr-D-Ala-Gly-Phe-Leu-Arg, which was synthesized in the Laboratory of Pep- tide Synthesis, Institute of Experimental Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR (Director M. I. Titov), and which was called dalargin. It differs from the N-terminal fragment of dinorphine in replacement of Gly by D-AIa in posi- tion 2. Dalargin has now been successfully used for the treatment of duodenal ulcer in man [3], but the precise mechanisms of its antiulcerative action have not been established. The aim of this investigation was to study the effect of dalargin on ornithine decarb- oxylase (ODC; ED 4.1.1.17) in homogenates of the duodenal ulcer from rats with experimental duodenal ulcer induced by cysteamine. EXPERIMENTAL METHOD Experiments were carried out on 150 male Wistar rats weighing 200-250 g. The animals were given a single subcutaneous injection of cysteamine hydrochloride (Fluka, Switzerland) in a dose of 350 mg/kg. Immediately thereafter and 12 h later the rats received an injec- tion of dalargin in doses of 12.5 (group i) and 5000 ~g/kg (group 2) or of physiological saline (group 3), also subcutaneously, 12 h later. Group 4 consisted of animals which re- ceived a subcutaneous injection of naloxone in a dose of i mg/kg simultaneously with dalar- gin in a dose of 12.5 pg/kg. Rats of group 5 received an injection of physiological saline only. Some rats were decapitated 24 h after the beginnln~ of the experiment, the duodenum was removed, and by means of a binocular loupe, the state of the mucosa was assessed. The parameters of ulcer formation were the ulcer index (UI), the frequency of involvement (FI), and the severity of the lesion (SL), which were determined by the method described pre- viously [2]. Activity of ODC was then determined in homogenates prepared from scrapings of the mucosa [Ii]. Some animals from each group were decapitated 6 h after the beginning of the experiment and their duodenum was taken for determination of ODC activity in the mucosa before the development of ulcers. ODC activity was determined by the method described pre- Institute of Experimental Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Eksperimental'noi Biolo- gii i Meditsiny, Vol. 103, No. 3, pp. 319-321, March, 1987. Original article submitted June i0, 1986. 356 0007-4888/87/0003-0356512.50 9 1987 Plenum Publishing Corporation