Eledoisin, which is isolated from an acetone extract of the posterior gland of the ocean Eledone moschata and E. aldrovandi and having a strong antihypertensive activity against a dog, is a physiologically active neuropeptide consisting of 11 amino acid residues (Erspamer, V., et al., Experientia, 18, 58, 1962). It has been obvious that the eledoisin shows a constricting activity of the ileum of a guinea pig other than an antihypertensive activity and also shows a specific action such as acceleration of salivary secretion of dog administered by intravenous injection.
Thereafter, the peptide having the same activities has been isolated from a skin of frog and this has been named physalaemin (Erspamer, V., et al. Experientia, 20, 489, 1964).
Such peptides were named tachykinin (tachy(=fast)kinin, something to contract quickly) against bradykinin (brady (=gradually)kinin, something to move gradually) because they have constricting activity against the ileum of a guinea pig quickly. Further, the chemical structure of substance P has been clarified based on the chemical structure of such peptides.
Though peptides classified into the tachykinin have been isolated thereafter one after another from the Amphibian class (Yasuhara, T., et al., Biomed. Res., 2, 613, 1981) and the Avian class (Conlon, J. M., et al., Regulatory Peptides, 20, 171, 1988), sialokinin only has been found out from a mosquito which has mediated yellow fever other than eledoisin from a invertebrate animal (Champagne, D. E. & Ribeiro. J. M.: Proc. Natl. Acad. Sci., USA, 91, 138, 1994).
At present, tachykinin has a common amino acid sequence represented by the following formula in the C-terminal of a peptide:
Phe-Xaa-Gly-Leu-Met-NH2 (SEQ ID NO: 6)
wherein, Xaa is aromatic amino acid (e.g., Phe, Tyr) and branched amino acid (e.g., Val, Ile). Tachykinin is used herein as a generic term of a physiologically active peptide indicating an intestine constricting activity, a hypotensive activity, a saliva secretion accelerating activity and the like. In such kinds of tachykinin, there are included aforementioned substance P, eledoisin, physalamine, neurokinin A, neurokinin B, kassinin and the like (SEIBUTUGAKU-JITEN (Ver. 4). Iwanami Shoten, 1997).
In this way, it has been expected to employ the tachykinin peptide as a basic chemical compound for developing a new medicine. In particular, since it has been considered that substance P has taken part in transmitting a pain as a transmitting substance of a primary sensory nerve, it has been expected and researched to develop as analgesics. Further, it has been expected to use practically a chemical reagent for elucidating an information processing mechanism in a nerve system of higher animals.
By the way, it is said that the posterior salivary gland of octopuses are venom gland since some of the salivary gland may include toxic substances such as tetrodotoxin known as fugu poison, and cephalotoxin that is a glycoprotein having an effect of numbing Crustaceans other than aforementioned eledoisin. Further, it has been known that they might include a biogenic amine group such as octopamine, serotonin, tyramine, noradrenaline, histamine, and acetylcholine and they might include an enzymatic group such as a proteolytic enzyme and hyaluronidase (Boucaud-Camou, E. & Boucher-Rodoni, R. 1983. Feeding and digestion in Cephalopods. In “The mollusca”, (Saleuddin, A. S. M. & Wilbur, K. M.), Academic press and New York). It, however, has not been reported that the tachykinin peptide other than eledoisin has been found. Further, though it has been discovered that eledoisin shows smooth muscle constricting activity, angiectatic activity, and antihypertensive activity to the mammals, it has not been discovered that eledoisin has a role to the octopus.
In this way, it is required to find out the tachykinin peptides from greater number of animal species, in order to obtain information which is useful for development of the medicines and for solving an information processing mechanism in a nerve system of higher animals based on research and the like of a structure-activity relationship by elucidating a species specificity of the peptides and a role of each of animal species about the tachykinin peptides.
Therefore, the object of the present invention is to provide the novel tachykinin peptide capable of being used as a chemical reagent for elucidating an information processing mechanism in a nerve system of higher animals and as a basic chemical compound in developing the medicines and the pesticides by finding out the novel tachykinin peptides, making clear the structure thereof, and further elucidating the physiologically activities thereof.
Further, the object of the present invention is to provide a method for producing the tachykinin peptide by identifying the precursor polypeptide of such tachykinin peptide and gene encoding thereof.