Structure-activity relationship of philanthotoxins--II. Effects on the glutamate gated ion channels of the locust muscle fibre membrane.
1. PTX-4.3.3, the synthetic product of the wasp toxin, delta-philanthotoxin, blocks the open, glutamate gated, ion channels of the locust muscle. 2. This block is accompanied by the appearance of double exponential distribution of the closed times frequency, and a decrease of the inverse relationship between the open and closed states. 3. The analogues with the shortened polyamine chain, PTX-4.3 and PTX-3.3, are less potent, trifluoromethyl-PTX-4.3.3 is a more potent analogue. 4. Yet, they still behave like PTX-4.3.3 as open ion-channel blockers. 5. Another analogue, without the aromatic nucleus, dephenol-PTX-4.3.3, proved to act in a different way. 6. This less potent analogue, doesn't block the open ion channels. 7. Most likely, the not-activation induced, non-competitive antagonism, caused by dephenol-PTX-4.3.3, has a modulatory effect on glutamate receptors. 8. Methyl-PTX-4.3.3 is also an open ion-channel blocker. However, at relatively low concentrations it has an agonistic-like effect, probably of a modulatory origin as well. 9. A long-term inhibition of PTX-4.3.3 applied at low concentrations also indicates that beside an open ion-channel block, also other inhibitory processes are involved.
Karst
H
H
Department of Pharmacology, University of Amsterdam, The Netherlands.
Piek
T
T
D000818:Animals; D006110:Grasshoppers; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008566:Membranes / Q000187:drug effects / Q000648:ultrastructure; D009132:Muscles / Q000187:drug effects* / Q000648:ultrastructure; D011073:Polyamines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors; D014862:Wasp Venoms / Q000633:toxicity*
D007473:Ion Channels; D011073:Polyamines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014862:Wasp Venoms; C069948:methyl-PTX-4.3.3; C069950:trifluoromethyl-PTX-4.3.3; C069952:dephenol-PTX-4.3.3; C034092:delta-philanthotoxin