Segmental synaptic depression caused by diisopropylphosphorofluoridate and sarin is reversed by thyrotropin-releasing hormone in the neonatal rat spinal cord.
The organophosphorus compounds diisopropylphosphorofluoridate (DFP) and isopropylmethylphosphonofluoridate (sarin) depressed the monosynaptic reflex (MSR) in spinal cords from 7- to 9-day-old male rats. The concentrations of DFP and sarin which depressed the MSR by nearly 50% were 100 microM and 100 nM, respectively. Simultaneous superfusion of the cords with thyrotropin-releasing hormone (TRH) with either DFP or sarin resulted in a reversal of the depression. The depression caused by DFP was reversed to 95% of control by 100 nM TRH whereas similar reversal of sarin-induced depression required a 10-fold greater concentration of TRH. The potentiating effect of TRH was not affected by atropine even at a high concentration (1 microM) although atropine easily reversed organophosphorus-induced depression of the MSR. It appears that reversal of organophosphorus-induced depression by TRH might occur through a noncholinergic, TRH-sensitive receptor mechanism and may be unrelated to acetylcholinesterase activity. This action represents a possible utility of TRH as an adjunct in organophosphorus toxicity.
Das Gupta
S
S
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Deshpande
S B
SB
Warnick
J E
JE
D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D002802:Cholinesterases / Q000032:analysis; D007531:Isoflurophate / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018025:Receptors, Thyrotropin-Releasing Hormone; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D012524:Sarin / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D009943:Organophosphorus Compounds; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D007531:Isoflurophate; D013973:Thyrotropin-Releasing Hormone; D001285:Atropine; D012524:Sarin; D002802:Cholinesterases