Toxi con, Vol . 19, No. 5, pp. 691- 699, 1981 . 0041- 0101/ 8l / 050691- OS 50200/ 0 Pr i nt ed in Gr eat Bri t ai n . ® 1981 Per gamon Pr ess Lt d . A TOXI N FROM THE VENOM OF THE MARI NE SNAI L CONUS GEOGRAPHUS WHI CH ACTS ON THE VERTEBRATE CENTRAL NERVOUS SYSTEM CRAI G CLARK, BALDOMERO M . OLI VERA Uni ver si t y of Ut ah, Depar t ment of Bi ol ogy, Sal t Lake Ci t y, Ut ah 84112, U .S.A . and LOURDES J . CRUZ Uni ver si t y of t he Phi l i ppi nes, Depar t ment of Bi ochem i st r y, Col l ege of Medi ci ne, Mani l a, Phi l i ppi nes ( Accept ed f or publ i cat i on 26 Mar ch 1981) CRAI GCLARK, BALDOMERO M . OLI VERA ând LOURDES I . CRU Z . A t OXi n f r omt he venomof t he mari ne snai l Conus geogr aphus whi ch act s on t he ver t ebr at e cent r al ner vous syst em . Toxi con 19, 691- 699, 1981 .-A t oxi n f r om t he venom of t he mari ne snai l , Conus geogr aphus Li nne, has been pur i f i ed to homogenei t y and char act er i zed. The t oxi n is a heat st abl e aci di c pr ot ei n wi t h an appar ent monomer mol . wt of 13, 000 . It has no det ect abl e t oxi ci t y to m i ce on i .p . i nj ect i on, but is a pot ent convul sant f ol l owi ng i nt r acer ebr al i nj ect i on . Thus, it is di st i nct f r omot her t oxi ns in t he venom whi ch act on t he per i pher al neur omuscul ar syst em. I NTRODUCTI ON THE GENUS Conus compr i ses sever al hundr ed speci es of pr edaci ous mari ne snai l s . Al l speci es t hat have been exam i ned pr oduce venoms to i mmobi l i ze t hei r pr ey . Ther e ar e t hr ee maj or f eedi ng t ypes in t he genus, wor meat er s ( ver m i vor ous) , mol l usc eat er s ( mol l usci vor ous) and fish eat er s ( pi sci vor ous) . The t oxi ci t y of Conus to man is wel l est abl i shed ; at l east t en human f at al i t i es have been r ecor ded ( KOHN, 1963) . A cor r el at i on has been est abl i shed bet ween t he t oxi ci t y of t hese venoms to ver t ebr at es and t hei r pr ey t ype . Al l pi sci vor ous speci es t est ed pr oduce venoms whi ch cause par al ysi s and deat h in m i ce if t he venomis i nj ect ed i .p. ; on t he ot her hand, mol l usci vorous and ver m i vor ous cone speci es pr oduce venoms whi ch ar e not st r ongl y t oxi c to m i ce by t hi s assay r out e ( WHYTE ar i d ENDEAN, 1962 ; ENDEAN and Ri J DKI N, 1965 ; KOHN et al ., 1960 ; CRUZ et al ., 1976) . However , t he venoms of at l east t wo speci es of mol l usc eat i ng Conus, i .e . Conus t ex t i l e and Conus mar mor eus ( KoxNet al ., 1960 ; CRUZ et al ., 1976) have been shown to be ext remel y t oxi c if i nt r oduced di r ect l y i nt o t he cent r al ner vous syst em of m i ce by i nt r acer ebr al or i nt r aci st er nal i nj ect i ons . Venoms of t he fish eat i ng cones ar e al so hi ghl y t oxi c if i nj ect ed i nt r acer ebr al l y i nt o m i ce. It has not been est abl i shed whet her t he cent r al ner vous syt em t oxi n in t hese l at t er venoms is t he s ame as t he agent whi ch is act i ve on i .p. i nj ect i on . Si nce mol l usc eat i ng speci es such as Conus t ex t i l e and Conus mar mor eus cont ai n a t oxi n whi ch is act i ve onl y upon i nt r acer ebr al i nj ect i on but not i .p . i nj ect i on, it seemed possi bl e t hat at l east t wo di f f er ent t oxi ns exi st in pi sci vor ous Conus venoms with di f f er ent modes of physi ol ogi cal act i vi t y . We have i nvest i gat ed t hi s quest i on usi ng t he venom of t he pi sci vor ous Conus whi ch has caused t he gr eat est number of human f at al i t i es, Conus geogr aphus . Thi s r epor t descr i bes t he i sol at i on and char act er i zat i on of a CNSt oxi n in Conus geogr aphus venom . The t oxi n is i nact i ve by t he i .p . r out e . 691