Charakterystyka endogennych inhibitorów enzymów rozkładających enkefaliny

• Autorzy: Sobocińska M. , Maćkiewicz Z.

Warianty tytułu

EN

Characteristic of the endogenous enkephalin degrading enzymes inhibitors

• Języki publikacji: PL

Abstrakty

EN

Management of acute and chronic pain has always been a key area of clinical research. Pain and stress stimulation may cause an increase in the level of endogenous opioids in the body. Endogenous enkephalins activate opioid receptors in the brain, leading to the analgesic effect. Enkephalinases inactivate endogenous opioids, abolishing their activity. Enkephalin degrading enzyme inhibitors (EIs) in turn inhibit these enzymes, preventing them from degrading endogenous enkephalins what leads to analgesia. The enkephalin degrading enzyme inhibitors seem to be promising analgesic agents [2]. Analgesic effect of EIs has been discovered recently and their therapeutic potential has not been effectively investigated yet. The main advantage of enkephalinase inhibitors is that they do not show adverse effects characteristic for opioids. EIs play an important role in modulating nociception, so they are potential agents for the treatment of acute and chronic pain. They often possess also additional antidiarrheal, antidepressant and anticancer properties [3]. The potential EIs targets appear to be aminopeptidase N (APN), dipeptidyl peptidase III (DPP III), angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) [4]. EIs may be broadly classified as endogenous and those that are obtained synthetically [4]. The purpose of this work is to present a review of endogenous enkephalinase inhibitors: sialorphin, opiorphin, and spinorphin. Sialorphin (Gln-His-Asn-Pro-Arg) is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. Sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin prevents spinal and renal NEP from breaking down substance P and Met-enkephalin in vitro. Sialorphin suppressed pain sensation for both chemical- -induced inflammation and acute physical pain [8, 9, 12]. Opiorphin (Gln-Arg-Phe-Ser-Arg) is an endogenous chemical compound first isolated from human saliva. Opiorphin is a natural analgesic. Opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase N. Opiorphin is closely related to the rat sialorphin peptide [12, 13, 19]. Spinorphin (Leu-Val-Val-Tyr-Pro-Trp-Thr) has been isolated from the bovine spinal cord as an endogenous inhibitor of enkephalin - degrading enzymes. Spinorphin is an antagonist of the P2X3 receptor and a weak partial agonist/antagonist of the FP1 receptor [24, 25, 26].

Słowa kluczowe

PL

inhibitory; inhibitory enzymów rozkładających enkefaliny; Els; endogenne inhibitory enzymów rozkładających enkefaliny; opiody; peptydy; ból; środki przeciwbólowe

EN

inhibitors; endogenous enkephalin degrading enzymes inhibitors; opioid; peptides; pain; analgesicagents

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Wiadomości Chemiczne
• Rocznik: 2014
• Tom: [Z] 68, 3-4
• Strony: 317--327
• Opis fizyczny: Bibliogr. 29 poz., schem., tab.

Twórcy

autor

Sobocińska M.

• Pracownia Chemii Polipeptydów Wydział Chemii, Uniwersytet Gdański ul. Wita Stwosza 63 80-308 Gdańsk

autor

Maćkiewicz Z.

• Pracownia Chemii Polipeptydów Wydział Chemii, Uniwersytet Gdański ul. Wita Stwosza 63 80-308 Gdańsk

Bibliografia

• [1] J. Dobrogowski, J. Wordliczek, Leczenie bólu, PZWL, Warszawa 2007.
• [2] Światowa Organizacja Zdrowia, Instytut Psychiatri Neurologii, Warszawa, 1997.
• [3] H. Lullmann, K. Mohr, L. Heun, D. Bieger, Color atlas of pharmacology, Thieme, 2005, s. 208.
• [4] V. Thanawala, J.V. Kadam, R. Ghosh, Curr. Drug Targets, 2008, 9, 887.
• [5] C. Rougeot, J.F. Huaulme, M.N. Ungeheuer, A. Wisner, E. Dufour, Patent, FP 1577320 T3.
• [6] P. Popik, E. Kamysz, J. Kreczko, M. Wróbel, Behav. Brain Res., 2010, 213, 88.
• [7] J. Wulfaenger, S. Niedling, D. Riemann, B. Seliger, Mol. Membr. Biol., 2008, 25 72.
• [8] A .Kubiak-Wlekły, Z.I. Niemir, Pol. Merk. Lek., 2009, 157, 51.
• [9] K. Nishimura, T. Hazato, Biochem. Bioph. Res. Commun., 1993, 194, 713.
• [10] G. Konieczny, A. Posadzy-Małaczyńska, A. Tykarski, Via Medica, 2006, 3, 140.
• [11] M. Messaoudi, D. Desor, A. Nejdi, C. Rougeot, Horm. Behav., 2004, 46, 684.
• [12] K.P. Davies, M. Tar, C. Rougeot, A. Melman, BJU Int, 2007, 99, 431.
• [13] C. Rougeot, M. Messaoudi, V Hermitte, A.G. Rigault, T. Blisnick, C. Dugave, D. Desor, F. Rougeon, PNAS 2003, 100, 8549.
• [14] M. Marini, L.G. Roda, Arch Oral Biol., 2000, 45, 775.
• [15] C. Rougeotf, F. Robert, L. Menz, J.F. Bisson, M. Messaoudi, J Physiol. Pharmacol., 2010, 61, 483.
• [16] A. Wisner, E. Dufour, M. Messaoudi, A. Nejdi, A. Marcel, M.N. Ungeheuer, C. Rougeot, Proc. Natl. Acad. Sci. USA, 2006, 103, 17979.
• [17] V. Thanawala, V.J. Kadam, R. Ghosh, Curr. Drug Targets, 2008, 9, 887.
• [18] C. Rougeot, I. Rosinski-Chupin, F. Rougeon, Biomed. Rev., 1998, 9, 17.
• [19] D.P. Dickinson, M. Thiesse, Curr. Eye Res., 1996, 15, 377.
• [20] C. Rougeot, M. Messaoudi, V. Hermitte, A.G. Rigault, T. Blisnick, C. Dugave, D. Desor, F. Rougeon, PNAS 2003, 100, 8549.
• [21] H. Javelot, M. Messaoudi, S. Garnier, C. Rougeot, J. Physiol. Pharmacol., 2010, 61, 355.
• [22] C. Rougeot , E. Dufour, S. Villard-Saussine, M.N. Ungeheuer, P. Jouannet, Patent, WO 2010/060995 A1.
• [23] L. Brkljačić, M. Sabalić, I. Salarić, I. Jerić, I. Alajbeg, I. Nemet, J. Chromatogr. B, Analyt. Technol. Biomed. Life Sci., 2011, 879, 3920.
• [24] C. Rougeot, F. Robert, L. Menz, J.F. Bisson, M. Messaoudi, J. Physiol. Pharmacol., 2010, 61, 483.
• [25] K. Nishimura, T. Hazato, Musai, 1993, 42,1497.
• [26] T.S. Liang, J.L. Gao, O. Fatemi, M. Lavigne, T.L. Leto, P.M. Murphy, J. Immunol., 2001, 167, 6609.
• [27] K. Jung, H. Moon, G. Lee, H. Lim, C. Park, Y. Kim, J. Med. Chem., 2007, 50, 4543.
• [28] G.A. Bezerra, E. Dobrovetsky, R. Viertlmayr, A. Dong, A. Binter, M. Abramić, P. Macheroux, S. Dhe-Paganon, K. Gruber, Proc. Natl. Acad. Sci. USA, 2012, 109, 6525.
• [29] M. Honda, H. Okutsu, T. Matsuura, Jpn. J. Pharmacol., 2001, 87, 261.