RT Journal Article
SR Electronic
T1 Allosteric inhibition of nicotinic acetylcholine receptors of vertebrates and insects by philanthotoxin.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 123
OP 130
VO 249
IS 1
A1 R Rozental
A1 G T Scoble
A1 E X Albuquerque
A1 M Idriss
A1 S Sherby
A1 D B Sattelle
A1 K Nakanishi
A1 K Konno
A1 A T Eldefrawi
A1 M E Eldefrawi
YR 1989
UL http://jpet.aspetjournals.org/content/249/1/123.abstract
AB The effects of pure philanthotoxin (PhTX), a component of the venom of the wasp Philanthus triangulum, were studied on nicotinic acetylcholine receptors (nAChRs) of vertebrates and insects so as to compare their sensitivities and the mechanism of action of PhTX. Electrophysiological techniques were used on frog muscles and cockroach thoracic ganglia and biochemical techniques were applied to membranes from Torpedo electric organ and honeybee brain. PhTX (1-20 microM) inhibited reversibly the indirectly elicited muscle twitch and reduced the endplate current peak amplitude and its decay time constant in a concentration-dependent manner. In patch clamp studies, PhTX (1-5 microM) when combined with acetylcholine, induced a concentration-dependent decrease in frequency of channel openings and in channel open and burst times. The cockroach fast coxal depressor neuron was inhibited by PhTX in a time- and voltage-dependent manner. The initial rate of binding of [3H]perhydrohistrionicotoxin to Torpedo nAChR in the presence of carbamylcholine was inhibited competitively by PhTX. Binding of alpha-[125I] bungarotoxin to electric organ and honeybee brain membranes was inhibited by PhTX. Binding of [3H]acetylcholine to the electric organ receptor was potentiated by low concentrations of PhTX but inhibited by high concentrations. PhTX, therefore, inhibits both vertebrate and insect nAChRs, which may be important molecular targets for its toxicity. It is suggested that PhTX at high concentration may have some competitive action on nAChR, but it acts mainly as a blocker of the ion channel of the nAChR in its open conformation.