動物起源の生物活性物質の解明

抄録

Biologically active materials were characterized chemically from various kinds of amphibian skin, and from the venom of wasps or spiders. The assay system employed for the biological activity on smooth muscle, were vaso-constriction and-delation, smooth muscle contraction and relaxation. Cytotrophic action including haemolysis, granulocyte degranulation, platelet aggregation, chemotaxis of leucocyte, and modulation of neural synaptic transmission were adopted for screening of the other materials. Many kinds of active peptide honologous to mammaliam peptide hormone, for example thyrotropin-releasing hormone (TRH), neurotensin, cholecystokinin (CCK), angiotensin, were found in high concentration from the methanol extract of the frog skin. A new cytotrophic peptide family was found both in frog skin and wasp venom. These peptides were rich in hydrophobic amino acids and basic ones. A peptide named mastoparan acts directly on the GTP binding protein as the hormone mimetic action and degranulates histamine granules of the mast cells. Another peptide revealing chemotactic activity for neutrophils acts directly on the FMLP receptor of the cells. These types of cytotrophic peptides modulate a cell signalling system via GTP-binding protein in such cells. Finally, over 15 kinds of neurotoxin were found from the spider venom which inhibit synaptic transmission of glutamate, both for lobster neuromuscular junction and mammaliam hippocampal neurons. A specific binding protein for this type of spider toxin was isolated from the bovin brain. The protein is a family of calreticulin previously isolated as a calcium regulating protein from sarcoplasmic reticulum in skeletal muscle.