Wyniki wyszukiwania - Biblioteka Nauki

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Charakterystyka endogennych inhibitorów enzymów rozkładających enkefaliny

100%

Sobocińska M. , Maćkiewicz Z.

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tom [Z] 68, 3-4

317--327

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].

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Charakterystyka stateryny - białka śliny zaangażowanego w utrzymywanie homeostazy jamy ustnej

80%

Jackiewicz-Barańska D. , Kamysz E. , Maćkiewicz Z.

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tom [Z] 62, 7-8

595-608

EN

Saliva is a gel resembling liquid, that acts almost as an organic tissue [1]. Saliva influences oral health through its non-specific physico-chemical properties [2]. It is composed of secretions from parotid, submandibular and sublingual glands, and smaller contributions come from minor salivary glands (e.g. palatal and labial). Saliva contains a number of proteins and polypeptides [2]. One of them is statherin a multifunctional 43-amino acid residue phosphominiprotein, containing vicinal phosphoserines at 2 and 3 positions and seven residues of tyrosine (Fig. 1) [7]. The relevant structural feature of statherin is N-terminal helix segment connected to a long poly--L-proline type II segment, which is followed by a short extended structure [14]. The gene for statherin is believed to be a single-copy gene and has been mapped to human chromosome 4q11-13 [20]. The statherin variants are SV1, SV2 and SV3 which comprise approx. 30% of the statherin family (Fig. 6). The ratios of statherin : SV1 and SV2 : SV3 are in both cases approx. 3 : 1. Statherin and SV2 are products of two different transcripts found in each of the major salivary gland. The variants SV1 and SV3 are derived by post-translational processing of statherin and SV2 [22]. Statherin is a multifunctional molecule that shows a high affinity for calcium phosphate minerals such as hydroxyapatite. It takes part in the calcium and phosphate transport during secretion in the salivary glands, is responsible for the protection and recalcification of tooth enamel, promotes selective initial bacterial colonization of enamel, and functions as a boundary lubricant on the enamel surface [38, 39]. Satherin levels of concentration in saliva could be in relation with the precancerous and cancerous lesions of the oral cavity [38]. The understanding of a profile and role of statherin has become important in medicine as the peptide could play a protective effect in oral cavity. However, the role and the functions of this peptide are still not well-know [38].

3

Statherin and its shortened analogues

61%

Wojciechowska I. , Kochańska B. , Stelmańska E. , Knap N. , Maćkiewicz Z. , Kupryszewski G.

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tom Vol. 72, nr 9

2098-2102

EN

Statherin is a 43-amino acid residue phosphominiprotein present in human parotid and submandibular saliva. It may take part in transport of calcium and phosphate and most probably is partly responsible for the protection and recalcification of tooth enamel. The solid phase synthesis of statherin and its three shorttened analoques: (1-15)statherin, [Ser(2), Ser(3)](1-15) statherin and [Asp(2), Asp(3)](1-15) statherin is presented. It was established that polyclonal antibodies directed against three shortened analoques showed affinity to synthetic statherin and statherin in saliva.