TRH fails to antagonize the acute paralytic effects of intrathecal dynorphin A and substance P antagonists in the rat.
Thyrotropin releasing hormone (TRH), which has been shown to improve neurologic recovery following cervical contusive spinal injury in cats, has also recently been reported to prevent the neuronal damage produced by the intrathecal (i.t.) administration of the substance P antagonist, spantide. Spantide and other substance P antagonists share with dynorphin A (DYN A)-related peptides the ability to produce an acute hindlimb paralysis after i.t. administration in the rat. By virtue of this effect, DYN A has been implicated in the secondary injury mechanisms that follow spinal trauma. Since TRH was shown to reduce the degree of histopathological injury caused by i.t. spantide, we investigated the ability of TRH to prevent or ameliorate the acute hindlimb paralysis produced by the i.t. injection of the substance P antagonists, (D-Arg1,D-Trp7,9,Leu11)-substance P (spantide) and (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-substance P, and DYN A in rats. In this study, TRH failed to improve motor function or survival following i.t. injections of substance P antagonists or DYN A.
Martinez-Arizala
A
A
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Long
J B
JB
Holaday
J W
JW
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology*; D006614:Hindlimb / Q000294:innervation; D008297:Male; D009068:Movement / Q000187:drug effects; D009132:Muscles / Q000294:innervation; D010243:Paralysis / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D010446:Peptide Fragments; D011994:Recombinant Proteins; D013373:Substance P; D013973:Thyrotropin-Releasing Hormone; C026843:dynorphin (1-13); D004399:Dynorphins; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-; C042867:spantide