Kassinin 是一種衍生自 Kassina 蛙的肽。Kassinin屬于速激肽家族的神經(jīng)肽。Kassinin分泌作為防御信號，并參與神經(jīng)肽信號傳導(dǎo)。

Kassinin is a peptide derived from the Kassina frog. It belongs to tachykinin family of neuropeptides. It is secreted as a defense response, and is involved in neuropeptide signalling.

Kassinin acetate是一種來源于卡司納蛙的速激肽，作為防御反應(yīng)分泌，參與神經(jīng)肽信號傳導(dǎo)，并在哺乳動物中顯示出對NK2比對NK1的選擇性。

Kassinin acetate, a tachykinin peptide derived from the Kassina frog, is secreted as a defense response, and is involved in neuropeptide signaling and shows selectivity for NK2 over NK1 in mammals.

定義
神經(jīng)肽的長度為3-40個氨基酸，可作為神經(jīng)遞質(zhì)。它們廣泛分布于中樞神經(jīng)系統(tǒng)和周圍神經(jīng)系統(tǒng)。

發(fā)現(xiàn)
神經(jīng)肽是由約翰·休斯博士和科斯特里茨博士于1975年發(fā)現(xiàn)的。它們是內(nèi)啡肽，內(nèi)在產(chǎn)生的嗎啡樣物質(zhì)，會在體內(nèi)產(chǎn)生一系列類似藥物的作用?？梢詮男蛄行畔?中鑒定神經(jīng)肽前體mRNA序列，并且得到的翻譯蛋白序列包括信號肽序列和一個或多個神經(jīng)肽。廣泛而復(fù)雜的一系列酶處理步驟，包括被激素或前蛋白轉(zhuǎn)化酶切割以及其他翻譯后修飾，在創(chuàng)建活性神經(jīng)肽之前就發(fā)生在翻譯后的蛋白質(zhì)序列上  2,3。

結(jié)構(gòu)特征
通過核磁共振（NMR）光譜研究了幾種來自軟體動物的類似神經(jīng)肽的構(gòu)象性質(zhì)。肽的N末端可變區(qū)中的氨基酸取代對溶液中反向轉(zhuǎn)化的種群具有顯著影響。通過使用兩個獨立的NMR參數(shù)測得的轉(zhuǎn)彎數(shù)，發(fā)現(xiàn)使用Helix aspersa的受體膜制劑與IC50值高度相關(guān)（r2 = 0.93和0.82）。這些結(jié)果表明，構(gòu)象集合降低了特定肽相對于特定受體4,5的有效濃度。

神經(jīng)肽Y與人肽相同，并且與禽胰多肽高度同源。神經(jīng)肽Y和禽胰多肽之間的同源性保留了維持三級結(jié)構(gòu)必不可少的所有殘基。結(jié)果表明，神經(jīng)肽保留了緊湊的三級結(jié)構(gòu)，其特征是在N末端的聚脯氨酸II類螺旋和C末端的a螺旋 6之間廣泛的疏水相互作用。

已經(jīng)通過許多孤兒受體之一發(fā)現(xiàn)了一些肽，這些受體是內(nèi)源性配體未知的受體，例如“類阿片受體樣1”（ORL1）。隨后，已闡明該ORL1受體的內(nèi)源性激動劑的結(jié)構(gòu)，一種稱為孤兒蛋白FQ或傷害感受蛋白的17個氨基酸的肽7。

行動方式
神經(jīng)肽是由神經(jīng)元作為細胞間信使釋放的肽。一些神經(jīng)肽充當(dāng)神經(jīng)遞質(zhì)，而另一些充當(dāng)激素。神經(jīng)肽既可以為我們提供支持，也可以為我們提供幫助。抗炎神經(jīng)肽可幫助我們減少皮膚發(fā)炎。神經(jīng)肽是自然產(chǎn)生的，可以在非常有限的時間內(nèi)與靶細胞膜受體在明確的作用位點相互作用。因此，大多數(shù)這些內(nèi)源性化合物的特征在于低的生物屏障滲透性和非常高的酶促降解敏感性。腦室內(nèi)或全身注射神經(jīng)肽Y（NPY）可使cast割的雌性大鼠血漿中的促黃體生成激素（LH）水平降低。6。

功能

生物功能，神經(jīng)肽控制著我們的情緒，能量水平，痛苦和愉悅感，體重以及解決問題的能力；它們還會形成記憶，情感行為，食欲和發(fā)炎，修復(fù)疤痕和皺紋并調(diào)節(jié)我們的免疫系統(tǒng)。這些活躍的大腦小信使實際上打開了皮膚7的細胞功能。因此，今天，與神經(jīng)肽系統(tǒng)相互作用的藥物設(shè)計是后基因組藥物化學(xué)研究最廣泛的途徑之一。

P物質(zhì)已被確定為負責(zé)傷害性信號傳遞的主要神經(jīng)肽。內(nèi)源性阿片類藥物是天然神經(jīng)肽，負責(zé)傷害性信號的調(diào)節(jié)（通常是抑制）。

免疫系統(tǒng)，當(dāng)它們被分泌時，它們會激活自然殺傷細胞（NK細胞），從而增強我們的免疫系統(tǒng)。

隨著內(nèi)啡肽的分泌越來越多，血管病變使收縮的血管恢復(fù)到正常狀態(tài)，使血液以正常方式流動。大多數(shù)成人疾病都始于血管堵塞。內(nèi)啡肽有助于改善血液循環(huán)。

內(nèi)啡肽通過去除超氧化物具有抗衰老作用。從呼吸進入人體的氧氣可以轉(zhuǎn)變?yōu)槌趸?。這是造成人類疾病和衰老的最大敵人之一。

抗壓力激素，應(yīng)對壓力的能力與我們體內(nèi)的內(nèi)啡肽水平成正比。

緩解疼痛的作用是，我們的神經(jīng)系統(tǒng)在接收到疼痛信號時會分泌神經(jīng)遞質(zhì)。一旦內(nèi)啡肽在疼痛的那一刻被釋放，內(nèi)啡肽就會與神經(jīng)元上的內(nèi)啡肽受體結(jié)合，從而阻止第一種神經(jīng)遞質(zhì)被分泌出來。

記憶力，神經(jīng)肽可以改善記憶力，因為它們可以使腦細胞保持年輕健康。

參考

1.     Hummon AB, Richmond TA, Verleyen P, Baggerman G, Huybrechts J, Ewing MA, Vierstraete E, Rodriguez-Zas SL, Liliane SL, Robinson GE (2006). From the genome to the proteome: uncovering peptides in the Apis brain. Science, 27(314):647-649.

2.     Rockwell NC, Krysan DJ, Komiyama T, Fuller RS (2002). Precursor processing by Kex2/Furin Proteases. Chem. Rev., 102:4525–4548.

3.     Von ER, Beck-Sickinger AG (2004). Biosynthesis of peptide hormones derived from precursor sequences. Curr. Med. Chem.,11:2651–2665.

4.     Edison AS, Espinoza E, Zachariah C (1999). Conformational Ensembles: The Role of Neuropeptide Structures in Receptor Binding. The Journal of Neuroscience., 19(15):6318-6326.

5.     Payza K, Greenberg MJ, Price DA (1989). Further characterization of Helix FMRFamide receptors: kinetics, tissue distribution, and interactions with the endogenous heptapeptides. Peptides, 10:657-661.

6.     Allen J, Novotný J, Martin J, Heinrich G (1987). Molecular structure of mammalian neuropeptide Y: Analysis by molecular cloning and computer-aided comparison with crystal structure of avian homologue. PNAS., 84:2532-2536.

7.     Guya J, Lia S,  Pelletier G (1988). Studies on the physiological role and mechanism of action of neuropeptide Y in the regulation of luteinizing hormone secretion in the rat. Regulatory Peptides., 23(2):209-216.

Definition
Dodecapeptide tachykinin that is kassinin is found in the central nervous system of the amphibian Kassina senegalensis. It is similar in structure and action to other tachykinins, but it is especially effective in contracting smooth muscle tissue and stimulating the micturition reflex.

Discovery
In 1964, Erspamer et al., first demonstrated the occurrence of bioactive peptide, kassinin in amphibian skin1. A biosynthetic precursor of kassinin cDNA encoding the novel kassinin analog (Thr2, Ile9)-kassinin was identified in skin secretion of amphibian2. In 1983, two new mammalian tachykinins, neurokinin A and neurokinin B, were discovered in the porcine spinal cord. Their pharmacological actions more closely resemble those of the amphibian tachykinin kassinin and the molluscan tachykinin eledoisin3.

Structural Characteristics
Tachykinins are among the most widely-studied families of regulatory peptides characterized by a highly-conserved C-terminal -Phe-X-Gly-Leu-Met amide motif, which also constitutes the essential bioactive core. Both the aqueous and lipid-induced structure of kassinin, has been studied by Rani et al., (2001). Water kassinin prefers to be in an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system, helical conformation is induced in the central core and C-terminal region (K4-M12) of the peptide. N-terminus though less defined also displays some degree of order and a possible turn structure. The conformation adopted by kassinin in the presence of DPC micelles is consistent with the structural motif typical of neurokinin-1 selective agonists and with that reported for eledoisin in hydrophobic environment4.

Mode of Action
In frog skin, tachykinins stimulate the ion transport, by interacting with NK1-like receptors which can be estimated by measuring the short-circuit current (SCC) value. Kassinin (NK2 preferring in mammals) increases the SCC5. Kassinin also induces concentration-related contractions of the longitudinal muscle of the mouse distal colon. Contractile responses to the tachykinins result from a direct activation of smooth muscle cells. Kassinin evokes a contractile response in the absence of external Ca2+ and their myogenic activity was, to some extent, resistant to the inhibitory effect of nifedipine (a calcium channel blocker). So an additional process, probably the release of an intracellularly bound Ca2+ store, participates in the mechanism by which kassinin contracts the mouse distal colon.  After desensitization of the mouse distal colon to Substance P (SP), the contractile activity provoked by SP was totally abolished whilst the responses evoked by kassinin were barely affected. These observations and other experimental findings indirectly support the assumption that the mouse distal colons possess different tachykinin-binding sites6.

Functions
Effect on rat urinary bladder - Synthetic replicates of kassinin are found to be active on rat urinary bladder smooth muscle at nanomolar concentrations2. Kassinin induces concentration-related contractions of the longitudinal muscle of the mouse distal colon.

Effect on endocrine pancreatic function - The effect of kassinin on endocrine pancreatic function was examined in the rat. Kassinin, injected intravenously in graded doses 10, 20, and 30 min before blood collection, significantly increased both plasma insulin and plasma glucagon in a dose-related fashion. The largest dose examined (10 µg) increased plasma insulin by 275% and plasma glucagon by 77% 7.    

Synthetic kassinin affects splanchnic circulation - Effects of intravenously administered synthetic kassinin on splanchnic circulation and exocrine pancreatic secretion was examined in six anesthetized dogs. Kassinin caused dose-related increases in the blood flow in superior mesenteric artery and portal vein, and produced an initial increase followed by a decrease in pancreatic blood flow, but did not affect the exocrine pancreatic secretion. This study suggests that kassinin functions as a neuropeptide controlling the splanchnic circulation in mammalian species8.

References

1.     Book : Handbook of chemical neuroanatomy. Chapter VI Neurokinin receptors in the CNS by Da-silva R, Mcleod AL, Krause JE.

2.     Wang L, Zhou M, Lynch L, Chen T, Walker B, Shaw C (2009). Kassina senegalensis skin tachykinins: Molecular cloning of kassinin and (Thr2, Ile9)-kassinin biosynthetic precursor cDNAs and comparative bioactivity of mature tachykinins on the smooth muscle of rat urinary bladder. Biochimie,  91(5): 613-619.

3.     Tan DP and Tsou K (1988). Differential Effects of Tachykinins Injected Intranigrally on Striatal Dopamine Metabolism. Journal of Neurochemistr, 51(5): 1333-1337.

4.     Rani CR, Lynn AM, Cowsik SM (2001). Lipid Induced Conformation of the Tachykinin Peptide Kassinin. Journal of Biomolecular Structure and Dynamics, 18 (4): 611-625.

5.     Lippe C, Bellantuon V, Ardizzone C, Cassano G (2004). Eledoisin and Kassinin, but not Enterokassinin, stimulate ion transport in frog skin. Peptides, 25(11): 1971-1975.

6.     Fontaine J and Lebrun P (1989). Contractile effects of substance P and other tachykinins on the mouse isolated distal colon. Br J Pharmacol, 96(3): 583–590.

7.     Gullner HG, Yajimsa  H, Harris V, Unger RH (1982). Kassinin: Stimulation of Insulin and Glucagon Secretion in the Rat. Endocrinology, 110 (4): 1246-1248.

8.     Doi R, Inoue K, Kogire M, Sumi S, Takaori K, Yun M, Yajima H, Tobe T (1988). Effects of synthetic kassinin on splanchnic circulation and exocrine pancreas in dogs. Peptides, 9(5): 1055-1058.