Daly J W, Gusovsky F, McNeal E T, Secunda S, Bell M, Creveling C R, Nishizawa Y, Overman L E, Sharp M J, Rossignol D P
Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Biochem Pharmacol. 1990 Jul 15;40(2):315-26. doi: 10.1016/0006-2952(90)90694-g.
Pumiliotoxin B (PTX-B) and a variety of congeneric alkaloids and synthetic analogs stimulated sodium flux and phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes. The effects of PTX-B and active congeners and analogs on sodium flux in synaptoneurosomes were potentiated markedly by scorpion venom (Leiurus quinquestriatus). In neuroblastoma cells, PTX-B and active congeners had no effect on sodium flux unless synergized by alpha-scorpion toxin or scorpion venom. Certain inactive congeners, lacking hydroxyl groups in the 6-alkylidene side chain, inhibited sodium flux elicited by PTX-B, scorpion venom, or the sodium channel activator batrachotoxin. Such inhibition appeared different from inhibition by local anesthetics, since pumiliotoxins, unlike local anesthetics, had little or no effect on binding of [3H]batrachotoxinin A benzoate to sodium channels. Thus, it appears likely that some "inactive" congeners bind to the PTX-B binding site, but do not activate sodium channels. In the absence of scorpion venom the stimulation of phosphoinositide breakdown in synaptoneurosomes was consonant with the stimulatory effects of these compounds on sodium flux through voltage-dependent sodium channels.
