[Mechanism of action of protirelin tartrate (TRH-T) on spinal motor neurons].
Thyrotropin releasing hormone (TRH), an endogenous tripeptide of the spinal cord, is being used in clinical trials for the treatment of neurological disorders involving the spinal function. Experiments have been carried out on rat lumbar motoneurons identified by their action potentials evoked by antidromic ventral root stimulation. Glass microelectrodes containing a concentrated KCl solution were used for intracellular electrophysiological findings while the specimen was continuously perfused with oxygenated saline solution. Previous experiments conducted in our laboratory had shown that TRH (50 mumol) has an intense depolarizing activity on frog motoneurons and that it is capable of considerably increasing excitatory postsynaptic potentials. In an ongoing trial in rat neurons we have observed how TRH produces slowly developing but persisting motoneuron depolarization characterized by steady action potential discharges. This phenomenon is different from the much more rapid and shorter effect of glutamate which is thought to be the excitatory neurotransmitter of these neurons. The capacity of TRH to generate a series of action potentials without any apparent "fatigue" is an interesting and unusual property. In order to explain this property we pharmacologically isolated the neurons by means of tetrodotoxin treatment and recorded their ionic conductance. While TRH was acting the conductance decreased considerably, indicating that synaptic signals are amplified in this new condition of the postsynaptic membrane. Voltage clamp studies have suggested that this decrease in conductance occurs within a range of relatively negative membrane potentials and probably consists in the blocking of voltage-dependent, tendentially repolarizing ion channels (perhaps potassium).(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology, Queen Mary and Westfield College, London, U.K.
D000818:Animals; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone
Meccanismo di azione della protirelina tartrato (TRH-T) sui motoneuroni spinali.