The action of philanthotoxin-343 and photolabile analogues on locust (Schistocerca gregaria) muscle.
The effects of philanthotoxin-343 (PhTX-343; tyrosyl-butanoyl-spermine) and photolabile analogues of this synthetic toxin on locust (Schistocerca gregaria) skeletal muscle have been investigated using whole muscle preparations (twitch contractions), single muscle fibres (excitatory postsynaptic currents (EPSCs)) and muscle membrane patches containing single quisqualate-sensitive glutamate receptors (qGluR). Analogues containing an azido group attached to either the butanoyl side-chain of PhTX-343 or as a substitute for the hydroxyl moiety of the tyrosyl residue were about 6 fold more potent antagonists than PhTX-343; those with an azido group located at the distal end of the toxin molecule were generally 2-3 fold less potent than PhTX-343. When these compounds were tested in subdued light, they were reversible antagonists of the muscle twitch, EPSC and qGluR. When a muscle was irradiated with U.V. during application of photolabile toxin combined with either neural stimulation of the muscle or L-glutamate application, antagonism of the twitch, EPSC and qGluR was complete and irreversible.
Sudan
H L
HL
Department of Life Science, University of Nottingham, UK.
Kerry
C J
CJ
Mellor
I R
IR
Choi
S K
SK
Huang
D
D
Nakanishi
K
K
Usherwood
P N
PN
D000818:Animals; D004355:Drug Stability; D004594:Electrophysiology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006110:Grasshoppers / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008027:Light; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D010636:Phenols / Q000494:pharmacology*; D011073:Polyamines / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology / Q000528:radiation effects
D007473:Ion Channels; D010636:Phenols; D011073:Polyamines; D017470:Receptors, Glutamate; D014118:Toxins, Biological; C074003:philanthotoxin 343; D018698:Glutamic Acid