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.