Antimitotic action of cornin as a biologically active polypeptide. I. Biochemical properties of cornin.

We succeeded in the extraction of a substance from beef cornea and rabbit muscle, that markedly inhibits mitosis of sea urchin eggs. The substance extracted from beef cornea is nondialysable and it can be separated into three fractions by DEAE-cellulose column. Although everyone of these fractions has an antimitotic action, that of fractions II and III is especially marked. These fractions are one of nucleoproteins that have adenine as base. The substance extracted from rabbit muscle is dialysable, and when it is fractionated through DEAE-cellulose column into three fractions, fraction I has no antimitotic effect but fractions II and III have it. Fraction II is one of nucleoproteins that have hypoxanthine as base. Carnin obtained from beef cornea or from rabbit muscle shows a typical protein wave, but after being treated with gas by passing oxygen through cornin solution the wave height is lowered. Carnin, however, is a very stable substance when kept dry in a desiccator. ∗PMID: 4221699 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 19, 1-9 (1965) ANTIMITOTIC ACTION OF CORNIN AS A BIOLOGICALLY ACTIVE POLYPEPTIDE I. BIOCHEMICAL PROPERTIES OF CORNIN* Isamu NISIDA and Tetuhide H. MURAKAMI Department of Physiology, Okayama University Medical School, Okayama, Japan Received for publication, January 12, 1965 On severing the third cranial nerve of the cat, NISIDA et at." noticed a curious phenomenon, a sudden contraction of dilated pupil in some hours after operation. It was demonstrated that this pupillo-contracting phenomenon was induced by a substance possessing a pupillo-contracting effect and that the substance was released from cornea. FUKUI successfully i~lated from the beef cornea this substance having pupillo-contracting effect and by its chemical analysis verified it to be a substance belonging to one of proteins, to which he gave a designation of "cornin". Later this cornin was found to have a stimulating effect on smooth muscle and a hypotensive action besides pupillo-contracting effect and a substance having similar properties was extracted also from rabbit muscle. This cornin was further verified to possess chemical properties different from those of biologically active polypeptides such as substance P, bradykinin, kalidin, and irin by the study of MIYAHARA and KADO. I~ addition, TOKuMoTo2'7 found that the distribution of cornin in vivo resembled closely to that of substance P, whereas HINO,t4 NISIDA et at. discovered that cornin has an antimitotic action on the early development of sea urchin eggs. In the course of study on biochemical properties and biological effects of cornin and substance P, it has been proved that cornin has a strong antimitotic activity while the substance P has a mitosis promoting effect. We know that there are in vivo such tissues that are readily regenerated showing much mitotic index and also such that are non-proliferating showing hardly any mitotic picture, but each of these tissues, when cultured in an appropriate medium, will proliferate well. These facts have led us to an assumption that there might be substances in vivo that regulate cell division and cell proliferation. This paper deals with biochemical properties of cornin, isolated from beef cornea and rabbit muscle, a substance that has been found to possess an anti* The work was completed while the authors held a maintenance grant from the Abbott Laboratories, Scientific Divisions, and grant in aid for Developmental Scientific Research of the Ministry of Education.