Effect of 4-aminopyridine on the postsynaptic action of polymyxin B.
Polymyxin B produces neuromuscular blockade by acting at pre- and postsynaptic sites. Its postsynaptic effect has been attributed either to blockade of open ionic channels or to the conversion of the end-plate receptor from a low to a high affinity state, i.e. to a state similar to the desensitized one caused by agonists. Since 4-aminopyridine inhibits agonist-induced end-plate receptor desensitization, we decided to investigate its effect on the postsynaptic action of polymyxin B. The experiments were carried out on the isolated rat diaphragm; miniature end-plate potentials (m.e.p.p.s) and carbachol-induced depolarization at the end-plate region were recorded with microelectrode techniques. Polymyxin B, 40 micrograms/ml reduced the amplitude of the m.e.p.p.s and suppressed them in about 30 min. 4-Aminopyridine completely antagonized this effect. Neostigmine did not restore the m.e.p.p.s suppressed by polymyxin B nor did 4-aminopyridine antagonize the effect of d-tubocurarine on these potentials. The carbachol-induced depolarization was blocked only partially by polymyxin B. 4-Aminopyridine B nearly completely antagonized this effect. The antagonistic effect of 4-aminopyridine on the postsynaptic action of polymyxin B favors the receptor desensitization' hypothesis.
Brazil
O V
OV
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil.
Fontana
M D
MD
Pavani
N J
NJ
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009045:Motor Endplate / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
D000631:Aminopyridines; D009467:Neuromuscular Depolarizing Agents; D011113:Polymyxins; D009388:Neostigmine; D002217:Carbachol; D015761:4-Aminopyridine; D011112:Polymyxin B; D014403:Tubocurarine