[Actin depolymerizing action by marine toxin, pectenotoxin-2].
Pectenotoxin-2 (PCTX-2), which is one of Diarrhetic Shellfish Poisoning (DSP), is a family of cyclic polyether macrolide toxin isolated from scallop Patinopecten yessoensis. Although PCTX-2 has a potent cytotoxic activities against several cancer cell lines, the biochemical activity of PCTX-2 has not been determined yet. To clarify the biochemical activity of PCTX-2 is the aime in this study. PCTX-2 inhibited the contractions elicited by 72.7 mM KCl or 1 microM phenyrephrine in a concentration dependent manner in the isolated rat aorta. In A10 cells, actin stressfiber in center but not in periphery of the cell was disrupted by PCTX-2 without any visible shape change. By monitoring fluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit the velocity and the degree of actin polymerization in a concentration dependent manner. In addition, PCTX-2 decreased viscosity of F-actin measured with falling ball viscometry. Stoichiometric analysis indicated that PCTX-2 forms 1:4 complex with G-actin. These results suggest that PCTX-2 is a potent natural actin depolymerizing compound with unique mode of action.
Hori
M
M
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Japan.
Matsuura
Y
Y
Yoshimoto
R
R
Ozaki
H
H
Yasumoto
T
T
Karaki
H
H
D000199:Actins / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D066298:In Vitro Techniques; D018942:Macrolides; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D011108:Polymers; D011714:Pyrans / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D000095702:Polyether Toxins
D000199:Actins; D000970:Antineoplastic Agents; D005663:Furans; D018942:Macrolides; D008387:Marine Toxins; D011108:Polymers; D011714:Pyrans; C098380:pectenotoxin 2; D000095702:Polyether Toxins