Kassinins

Introduction

Kassinin, a member of tachykinin peptides family, a dodecapeptide isolated from the skin of the african frog, Kassina senegalensis, is similar to substance P (SP) in structure and biological activity. Kassinin and SP share an identical sequence of three amino acids at the C-terminus. Both kassinin and SP stimulate the secretion of growth hormone, prolactin and follicle-stimulating hormone in rats, suggesting the physiological role of kassinin as a neuropeptide. Kassinin shares with all other known tachykinins the C-terminal pentapeptide (with the unimportant differencethat it has a Val residue at position 4 from the C-terminus: -Phe-X-Gly-Leu-Met-NH2, which also constitutes the essential bioactive core), but differs markedly from the other members the family in the N-moiety of the molecule.

Mechanism of kassinins

Tachykinins interact with three G protein-coupled receptors (GCPRs): NK1, NK2, and NK3 showing higher affinity for SP, Neurokinin A and Neurokinin B, respectively. Kassinin is specific agonist of NK2 and NK3 receptors, in mammals. In frog skin, tachykinins stimulate ion transport and are estimated by measuring short circuit current (SCC) values by interacting with NK1-like receptors. Kassinin (NK2 prefers mammals) increases SCC. In addition, kassinin also induced concentration of the relevant contractions of longitudinal muscle of the mouse distal colon. Response to contraction of tachykinins is caused by the direct activation of smooth muscle cells. Shrinkage reaction is caused by the kassinin in the absence of external Ca²⁺, and their myogenic activity, to some degree, resistant the inhibitory effect of nifedipine (calcium channel blockers). Therefore, an additional process, possibly the intracellular binding of Ca²⁺ stores, is involved in the mechanism of kassinin contracting the distal colon of mice. After desensitization of the distal colon of the mouse to SP, the contractile activity caused by SP was completely eliminated, and the reaction caused by carcinine was hardly affected. These observations and other experimental results indirectly support the hypothesis that the distal colon of mice has different tachykinin binding sites.

Application of kassinins

Kassinin possessed the entire spectrum of biological activity peculiar to the tachykinins. However, among the tachykinins examined, kassinin is the worst stimulant and weakest antihypertensive agent in saliva, and shows very strong stimulating effects on different smooth muscle preparations, especially on isolated preparations of urinary bladder. In addition, the effect of kassinin on endocrine pancreatic function was examined in the rat. Furthermore, kassinin functions as a neuropeptide controlling the splanchnic circulation in mammalian species.

References

1. Erspamer, G. F., Erspamer, V., & Piccinelli, D. (1980). Parallel bioassay of physalaemin and kassinin, a tachykinin dodecapeptide from the skin of the African frog Kassina senegalensis. Naunyn-Schmiedeberg’s archives of pharmacology, 311(1), 61-65.
2. Lippe, C., Bellantuono, V., Ardizzone, C., & Cassano, G. (2004). Eledoisin and Kassinin, but not Enterokassinin, stimulate ion transport in frog skin. Peptides, 25(11), 1971-1975.
3. Carballo-Pacheco, M., Ismail, A. E., & Strodel, B. (2015). Oligomer formation of toxic and functional amyloid peptides studied with atomistic simulations. The Journal of Physical Chemistry B, 119(30), 9696-9705.
4. Tanaka, K., Hashida, S., Kohno, T., Mohri, Z., Murakami, Y., & Ishikawa, E. (1989). Novel and sensitive noncompetitive enzyme immunoassay for kassinin in rat plasma. Experientia, 45(5), 470-472.