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Hideki Ono - One of the best experts on this subject based on the ideXlab platform.
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spinal cord injury specific depression of Monosynaptic spinal Reflex transmission by l 5 hydroxytryptophan results from loss of the 5 ht uptake system and not 5 ht receptor supersensitivity
Experimental Neurology, 2006Co-Authors: Motoko Honda, Mitsuo Tanabe, Hideki OnoAbstract:Abstract We studied changes in the spinal segmental Reflex and serotonergic (5-HT) responses in rats after spinal cord injury (SCI) produced by the weight-dropping method at the T8 level. The spinal Monosynaptic Reflex amplitude (MSR) was recorded from the L5 ventral root following stimulation of the ipsilateral L5 dorsal root. The 5-HT precursor l -5-hydroxytryptophan (L-5-HTP) depressed MSR in the spinal cord injured rats but not in normal rats. We investigated whether the SCI-specific depression of MSR by L-5-HTP was attributable to postsynaptic supersensitivity of 5-HT receptors or presynaptic loss of the 5-HT uptake system. Sumatriptan, a selective 5-HT1B/1D receptor agonist that is not taken up by 5-HT transporters, depressed the MSR similarly in both SCI and normal rats, suggesting that SCI resulted in the loss of 5-HT terminals and not postsynaptic supersensitivity of 5-HT receptors.
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endogenously released 5 hydroxytryptamine depresses the spinal Monosynaptic Reflex via 5 ht1d receptors
European Journal of Pharmacology, 2004Co-Authors: Motoko Honda, Keiko Imaida, Mitsuo Tanabe, Hideki OnoAbstract:Abstract In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT 1B receptors mediate the Monosynaptic Reflex depression induced by exogenously applied 5-HT that was formed from the precursor l -5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by dl -p-chloroamphetamine, on spinal Reflexes. dl -p-Chloroamphetamine depressed the Monosynaptic Reflex and increased the polysynaptic Reflex. The depletion of 5-HT abolished the Monosynaptic Reflex depression, but the increase in polysynaptic Reflexes was maintained, suggesting that endogenous 5-HT released by dl -p-chloroamphetamine mediates depression of the Monosynaptic Reflex in the spinal cord. The depression of the Monosynaptic Reflex was antagonized by GR127935 ( N -[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT 1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT 1D receptor antagonist) but not by isamoltane (5-HT 1B receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses Monosynaptic Reflex transmission via 5-HT 1D receptors.
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Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal Reflex transmission through 5-HT2 receptors
European Journal of Pharmacology, 2002Co-Authors: Motoko Honda, Takashi Nishida, Hideki OnoAbstract:The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of Monosynaptic Reflex potentials by inhibiting the facilitatory descending serotonergic influences in the spinal cord. Interestingly, the structure of cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In the present study, we attempted to elucidate the relationship between 5-HT(2) receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline, cyproheptadine and ketanserin on the spinal Reflexes. Cyclobenzaprine, amitriptyline, cyproheptadine, and ketanserin significantly inhibited facilitatory effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on flexor Reflexes and mono- and polysynaptic spinal Reflex potentials in spinalized rats. In intact rats, these drugs significantly reduced the mono- and polysynaptic Reflex potentials. 5-HT depletion significantly prevented the depression of the spinal Reflex potentials induced by these drugs. These results suggest that the inhibitory effects of cyclobenzaprine, amitriptyline, and cyproheptadine on mono- and polysynaptic Reflex potentials are due to the inhibition of descending serotonergic systems through 5-HT(2) receptors in the spinal cord.
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no involvement of 5 ht7 or 5 ht1d receptors in the r 8 oh dpat induced depression of the Monosynaptic Reflex in spinalized rats
European Journal of Pharmacology, 2001Co-Authors: Motoko Honda, Hideki OnoAbstract:(R)-8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) depressed the Monosynaptic Reflex. This effect was not antagonized by 5-HT(1A) receptor antagonists. We examined whether 5-HT(1D) and 5-HT(7) receptors are involved in (R)-8-OH-DPAT-induced inhibition of the Monosynaptic Reflex in spinalized rats. Pretreatment with methiothepin and mesulergine, but not clozapine, inhibited (R)-8-OH-DPAT-induced Monosynaptic Reflex depression. Pretreatment with 2a-(4-phenyl-1,2,3,6-tetrahydropyridal)butyl)-2a,3,4,5-tetrahydrobenzo[c,d]indol-2(1H)-one (DR4004) and (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrolidine (SB-269970), new selective 5-HT(7) receptors antagonists, and N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide (GR127935), a selective 5-HT(1D) receptor antagonist, had no effect on (R)-8-OH-DPAT-induced depression. These results suggested that 5-HT(7) and 5-HT(1D) receptors are not involved in (R)-8-OH-DPAT-induced Monosynaptic Reflex depression.
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Method for recording spinal Reflexes in mice: effects of thyrotropin-releasing hormone, DOI, tolperisone and baclofen on Monosynaptic spinal Reflex potentials.
Japanese journal of pharmacology, 2001Co-Authors: H Okada, M Honda, Hideki OnoAbstract:Mice were used to record the spinal Reflex potentials and to examine the effects of some drugs upon them. In anesthetized mice, laminectomy was performed in the lumbo-sacral region, and Monosynaptic Reflex potential (MSR) and polysynaptic Reflex potential were recorded from the L5 ventral root after stimulation of the L5 dorsal root. Thyrotropin-releasing hormone (TRH) and 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) produced transient and long-lasting increases in the MSR amplitude, respectively. Tolperisone hydrochloride and baclofen produced transient and long-lasting MSR depressions, respectively. These results show that mice can be used to record spinal Reflex potentials, and that it may be possible to study the spinal cord function of mutant and knockout mice using this method.
Motoko Honda - One of the best experts on this subject based on the ideXlab platform.
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spinal cord injury specific depression of Monosynaptic spinal Reflex transmission by l 5 hydroxytryptophan results from loss of the 5 ht uptake system and not 5 ht receptor supersensitivity
Experimental Neurology, 2006Co-Authors: Motoko Honda, Mitsuo Tanabe, Hideki OnoAbstract:Abstract We studied changes in the spinal segmental Reflex and serotonergic (5-HT) responses in rats after spinal cord injury (SCI) produced by the weight-dropping method at the T8 level. The spinal Monosynaptic Reflex amplitude (MSR) was recorded from the L5 ventral root following stimulation of the ipsilateral L5 dorsal root. The 5-HT precursor l -5-hydroxytryptophan (L-5-HTP) depressed MSR in the spinal cord injured rats but not in normal rats. We investigated whether the SCI-specific depression of MSR by L-5-HTP was attributable to postsynaptic supersensitivity of 5-HT receptors or presynaptic loss of the 5-HT uptake system. Sumatriptan, a selective 5-HT1B/1D receptor agonist that is not taken up by 5-HT transporters, depressed the MSR similarly in both SCI and normal rats, suggesting that SCI resulted in the loss of 5-HT terminals and not postsynaptic supersensitivity of 5-HT receptors.
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endogenously released 5 hydroxytryptamine depresses the spinal Monosynaptic Reflex via 5 ht1d receptors
European Journal of Pharmacology, 2004Co-Authors: Motoko Honda, Keiko Imaida, Mitsuo Tanabe, Hideki OnoAbstract:Abstract In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT 1B receptors mediate the Monosynaptic Reflex depression induced by exogenously applied 5-HT that was formed from the precursor l -5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by dl -p-chloroamphetamine, on spinal Reflexes. dl -p-Chloroamphetamine depressed the Monosynaptic Reflex and increased the polysynaptic Reflex. The depletion of 5-HT abolished the Monosynaptic Reflex depression, but the increase in polysynaptic Reflexes was maintained, suggesting that endogenous 5-HT released by dl -p-chloroamphetamine mediates depression of the Monosynaptic Reflex in the spinal cord. The depression of the Monosynaptic Reflex was antagonized by GR127935 ( N -[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT 1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT 1D receptor antagonist) but not by isamoltane (5-HT 1B receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses Monosynaptic Reflex transmission via 5-HT 1D receptors.
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Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal Reflex transmission through 5-HT2 receptors
European Journal of Pharmacology, 2002Co-Authors: Motoko Honda, Takashi Nishida, Hideki OnoAbstract:The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of Monosynaptic Reflex potentials by inhibiting the facilitatory descending serotonergic influences in the spinal cord. Interestingly, the structure of cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In the present study, we attempted to elucidate the relationship between 5-HT(2) receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline, cyproheptadine and ketanserin on the spinal Reflexes. Cyclobenzaprine, amitriptyline, cyproheptadine, and ketanserin significantly inhibited facilitatory effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on flexor Reflexes and mono- and polysynaptic spinal Reflex potentials in spinalized rats. In intact rats, these drugs significantly reduced the mono- and polysynaptic Reflex potentials. 5-HT depletion significantly prevented the depression of the spinal Reflex potentials induced by these drugs. These results suggest that the inhibitory effects of cyclobenzaprine, amitriptyline, and cyproheptadine on mono- and polysynaptic Reflex potentials are due to the inhibition of descending serotonergic systems through 5-HT(2) receptors in the spinal cord.
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no involvement of 5 ht7 or 5 ht1d receptors in the r 8 oh dpat induced depression of the Monosynaptic Reflex in spinalized rats
European Journal of Pharmacology, 2001Co-Authors: Motoko Honda, Hideki OnoAbstract:(R)-8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) depressed the Monosynaptic Reflex. This effect was not antagonized by 5-HT(1A) receptor antagonists. We examined whether 5-HT(1D) and 5-HT(7) receptors are involved in (R)-8-OH-DPAT-induced inhibition of the Monosynaptic Reflex in spinalized rats. Pretreatment with methiothepin and mesulergine, but not clozapine, inhibited (R)-8-OH-DPAT-induced Monosynaptic Reflex depression. Pretreatment with 2a-(4-phenyl-1,2,3,6-tetrahydropyridal)butyl)-2a,3,4,5-tetrahydrobenzo[c,d]indol-2(1H)-one (DR4004) and (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrolidine (SB-269970), new selective 5-HT(7) receptors antagonists, and N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide (GR127935), a selective 5-HT(1D) receptor antagonist, had no effect on (R)-8-OH-DPAT-induced depression. These results suggested that 5-HT(7) and 5-HT(1D) receptors are not involved in (R)-8-OH-DPAT-induced Monosynaptic Reflex depression.
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differential effects of r and s 8 hydroxy 2 di n propylamino tetralin on the Monosynaptic spinal Reflex in rats
European Journal of Pharmacology, 1999Co-Authors: Motoko Honda, Hideki OnoAbstract:We examined the effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the Monosynaptic spinal Reflex in rats. In intact rats, (R)-8-OH-DPAT (10 microg/kg, i.v.) enhanced the amplitude of the Monosynaptic Reflex, whereas at 100 microg/kg, it reduced the amplitude. (S)-8-OH-DPAT enhanced the Monosynaptic Reflex dose-dependently. In spinalized rats, (R)-8-OH-DPAT produced dose-dependent inhibition, but the (S)-enantiomer did not affect the Monosynaptic Reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited (R)-8-OH-DPAT-induced Monosynaptic Reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of (R)-8-OH-DPAT. These pretreatment regimens had no effect on the Monosynaptic Reflex depression produced by the (R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited (S)-8-OH-DPAT-induced Monosynaptic Reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT1A receptors and the descending serotonergic system are involved in the stimulatory effect of (R)-8-OH-DPAT on the Monosynaptic Reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via alpha1-adrenoceptors, are involved in the effect of the (S)-enantiomer on this Reflex.
Rodolfo Delgadolezama - One of the best experts on this subject based on the ideXlab platform.
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tonically active α5gabaa receptors reduce motoneuron excitability and decrease the Monosynaptic Reflex
Frontiers in Cellular Neuroscience, 2017Co-Authors: Martha Cantobustos, Emanuel Loezaalcocer, Carlos A Cuellar, Paulina Osuna, David Eliasvinas, Vinicio Granadossoto, Elias Manjarrez, Ricardo Felix, Rodolfo DelgadolezamaAbstract:Motoneurons, the final common path of the central nervous system, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we show that extrasynaptic α5 subunit-containing GABAA receptors (α5GABAAR) co-localize with choline acetyltransferase (ChAT) suggesting that these receptors are expressed in motoneurons. In these cells, α5GABAA receptors may be activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the Monosynaptic Reflex induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.
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pre and postsynaptic modulation of Monosynaptic Reflex by gabaa receptors on turtle spinal cord
The Journal of Physiology, 2010Co-Authors: Wendy Bautista, Justo Aguilar, Jose Emanuel Loezaalcocer, Rodolfo DelgadolezamaAbstract:There is growing evidence that activation of high affinity extrasynaptic GABAA receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABAA receptors mediating tonic inhibition participate in the modulation of Monosynaptic Reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a dorsal root depressed the test Monosynaptic Reflex (MSR) at long condition–test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABAA as it was completely blocked by 20 μm picrotoxin (PTX) or bicuculline (BIC) or 1 μm gabazine, simultaneously depressing the dorsal root potential (DRP) without MSR facilitation. Interestingly 100 μm picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABAA receptors, affects receptor subtypes with α4/6 subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of α4/6 GABAA receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABAA mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABAA receptors located at the motoneurones and primary afferents might produce tonic inhibition of Monosynaptic Reflex, and (3) GABAA receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation.
Shripad B Deshpande - One of the best experts on this subject based on the ideXlab platform.
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involvement of ampa receptors for mesobuthus tamulus pocock venom induced depression of Monosynaptic Reflex in neonatal rat spinal cord in vitro
Indian Journal of Experimental Biology, 2011Co-Authors: Amar N Maurya, Shripad B DeshpandeAbstract:Glutamate is a putative neurotransmitter at Ia-alpha motoneuron synapse in the spinal cord and mediate the action via N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. Since NMDA receptors are not involved in M. tamulus Pocock (MBT) venom-induced depression of spinal Monosynaptic Reflex (MSR), the present study was undertaken to evaluate the role of AMPA receptors in mediating the depression of MSR by MBT venom. The experiments were performed on isolated hemisected spinal cord from 4-6 day old rats. Stimulation of a dorsal root with supramaximal voltage evoked MSR and polysynaptic Reflex (PSR) potentials in the corresponding segmental ventral root. Superfusion of MBT venom (0.3 microg/ml) depressed the spinal Reflexes in a time-dependent manner. The maximum depression of MSR(approximately 66%) was seen at 10 min and it was 25 min for PSR (approximately 75%). The time to produce 50% depression of MSR and PSR was 6.7+/- 1.5 and 10.8 +/- 2.6 min, respectively. Pretreatment of the cords with 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 0.1 microM), an AMPA receptor antagonist, blocked the venom-induced depression of MSR but not PSR. The results indicate that venom-induced depression of MSR is mediated via AMPA receptors.
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5 ht induced depression of the spinal Monosynaptic Reflex potential utilizes different types of 5 ht receptors depending on mg2 availability
Pharmacological Reports, 2009Co-Authors: Shripad B Deshpande, Amar N Maurya, Jitendra SinghAbstract:Abstract Receptor subtypes involved in the 5-hydroxytryptamine (5-HT)-induced depression of synaptic transmission in neonatal rat spinal cords in vitro were evaluated in the absence or presence of Mg 2+ in the medium. Stimulation of a dorsal root evoked Monosynaptic Reflex potential (MSP) and polysynaptic Reflex potential (PSP) in the segmental ventral root in Mg 2+ -free medium where the voltage-dependent blockade of NMDAreceptors is absent. The 5-HT (0.3–50 μM) in the Mg 2+ -free medium depressed the MSPand PSP in a concentration-dependent manner. At 30 μM of 5-HT, the depression was 57% and 95% for MSP and PSP, respectively, and no further depression was seen at 50 μM. The 5-HT-induced depression of the Reflexes in the Mg 2+ -free medium was blocked by ondansetron (5-HT 3 receptor antagonist), but not by spiperone (5-HT 2A/2C antagonist). In the Mg 2+ -free medium, phenylbiguanide (5-HT 3 agonist) also depressed the MSPand PSP in a concentration-dependent manner and was blocked by ondansetron. Addition of Mg 2+ (1.3 mM) to the medium abolished the PSP and decreased the MSPby 30%. In the presence of Mg 2+ , 5-HT (1–50 μM) also depressed the MSP in a concentration-dependent manner. At 10 μM of 5-HT, there was approximately 20% depression and at 50 μM the depression was 100%. The 5-HT-induced depression of MSP in the Mg 2+ -containing medium was antagonized by spiperone (p 3 receptors in the Mg 2+ -free medium and 5-HT 2A/2C in the presence of Mg 2+ when NMDA receptors are in the closed state.
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analogs of thyrotropin releasing hormone in potentiating the spinal Monosynaptic Reflex in vitro
European Journal of Pharmacology, 1994Co-Authors: Shripad B Deshpande, J E WarnickAbstract:Abstract The efficacy of thyrotropin-releasing hormone (TRH) and its analogs to potentiate the spinal Monosynaptic Reflex was studied in isolated cords. The analogs examined were L -pyro-2-aminoadipyl-histidyl-thizolidine-4-carboxyamide (MK-771); pyroglutamyl-histidyl-prolineamide (TRH); pyroglutamyl- L -histidyl-3,3′-dimethyl-prolineamide (RX77368); (3-methyl-His 2 )TRH (methyl-TRH); γ-buturolactone-γ-carbonyl-histidyl-prolineamide citrate (DN-1417); pyroglutamyl-histidyl-proline (TRH-free acid); and histidyl-proline- diketopiperazine (cyclo(His-Pro)). The TRH analogs potentiated the Monosynaptic Reflex in a dose-dependent manner and the maximal potentiation occurred at about 1 μM. TRH-free acid potentiated the Monosynaptic Reflex but the maximal potentiation occurred at 100 times the TRH concentrations. Cyclo(His-Pro) was totally ineffective. The concentration required to potentiate the Monosynaptic Reflex by 50% of the maximal response (EC 50 ) was taken as an index for comparing various analogs in relation to TRH. The EC 50 values of the analogs did not differ significantly from each other. However, the ratio of the mean value of an analog to that of TRH was of the following order: MK-771 (N- and C-terminally altered) ⩾ TRH ⩾ DN-1417 (N-terminal) ⩾ methyl-TRH ⩾ RX77368 (C-terminal) > > > TRH-free acid. Cyclo(His-Pro) was ineffective.
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thyrotropin releasing hormone induced potentiation of spinal Monosynaptic Reflex in rats in vitro
Indian Journal of Experimental Biology, 1993Co-Authors: Shripad B Deshpande, J E WarnickAbstract:Superfusion of thyrotropin-releasing hormone (TRH) in neonatal rat spinal cord in vitro produced dose (0.01-1.00 microM) dependent potentiation of Monosynaptic Reflex (MSR) which was maximum (44% of control) at 1 microM of TRH. But no ventral root depolarization was observed with TRH (1 microM) although potassium concentration out side ([K+]0) when increased produced a depolarization at the magnitude of 0.2 mV/mM of [K+]0. TRH-induced potentiation of MSR was not altered in spinal cords, obtained from the animals pretreated with 5,7-dihydroxytryptamine or 6-hydroxydopamine. Neither serotonin antagonists (spiperone, ketanserin, cyproheptadine or 3-troponyl-indole-3-carboxylate) nor adrenergic antagonists (phentolamine or haloperidol) could attenuate TRH-induced potentiation. Inhibition of MSR observed in the spinal cord elicited by stimulating the adjacent dorsal root was unaffected by TRH. The results suggest that, TRH potentiates MSR by directly acting on the motoneurons, without involving presynaptic serotonergic or catecholaminergic neuronal systems or the disinhibition of pre- or post-synaptic inhibition in the spinal cord.
J E Warnick - One of the best experts on this subject based on the ideXlab platform.
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analogs of thyrotropin releasing hormone in potentiating the spinal Monosynaptic Reflex in vitro
European Journal of Pharmacology, 1994Co-Authors: Shripad B Deshpande, J E WarnickAbstract:Abstract The efficacy of thyrotropin-releasing hormone (TRH) and its analogs to potentiate the spinal Monosynaptic Reflex was studied in isolated cords. The analogs examined were L -pyro-2-aminoadipyl-histidyl-thizolidine-4-carboxyamide (MK-771); pyroglutamyl-histidyl-prolineamide (TRH); pyroglutamyl- L -histidyl-3,3′-dimethyl-prolineamide (RX77368); (3-methyl-His 2 )TRH (methyl-TRH); γ-buturolactone-γ-carbonyl-histidyl-prolineamide citrate (DN-1417); pyroglutamyl-histidyl-proline (TRH-free acid); and histidyl-proline- diketopiperazine (cyclo(His-Pro)). The TRH analogs potentiated the Monosynaptic Reflex in a dose-dependent manner and the maximal potentiation occurred at about 1 μM. TRH-free acid potentiated the Monosynaptic Reflex but the maximal potentiation occurred at 100 times the TRH concentrations. Cyclo(His-Pro) was totally ineffective. The concentration required to potentiate the Monosynaptic Reflex by 50% of the maximal response (EC 50 ) was taken as an index for comparing various analogs in relation to TRH. The EC 50 values of the analogs did not differ significantly from each other. However, the ratio of the mean value of an analog to that of TRH was of the following order: MK-771 (N- and C-terminally altered) ⩾ TRH ⩾ DN-1417 (N-terminal) ⩾ methyl-TRH ⩾ RX77368 (C-terminal) > > > TRH-free acid. Cyclo(His-Pro) was ineffective.
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Biphasic action of sarin on Monosynaptic Reflex in the neonatal rat spinal cord in vitro
Archives of Toxicology, 1993Co-Authors: J E Warnick, S. B. Deshpande, Q. Z. Yang, S. Das GuptaAbstract:The action of sarin, an organophosphorus (OP) compound, was examined in vitro for its effects on the spinal Monosynaptic Reflex (MSR) in neonatal rats. The effects of sarin were biphasic, i.e. facilitation at lower concentrations (2–20 nM) followed by depression of the MSR at concentrations above 30 nM. Facilitation of MSR was maximal (150% of control) at 20 nM sarin. The depression of MSR was maximal (70% of control) at 200 nM sarin, with half maximal inhibition occurring at 90 nM sarin. Atropine (200–500 nM) effectively reversed the depression caused by sarin, while pretreatment with low concentrations of atropine (10 nM) completely blocked the depression otherwise observed with sarin. Benactyzine was also effective in preventing sarin-induced depression, while pirenzepine was less effective. The nicotinic blocking agents tubocurarine and mecamylamine were, however, ineffective in preventing or reversing sarin-induced depression. The facilitation of MSR seen with lower concentrations (2–20 nM) correlated well with the blockade of late phase inhibition (between 30 and 50 ms conditioning-test interval) elicited in spinal cord by stimulating the adjacent dorsal root at various condition-test intervals, which has been shown elsewhere to be sensitive to bicuculline (Deshpande and Warnick 1988). Thus it is speculated that sarin at lower concentrations blocks GABA transmission, producing facilitation, and at higher concentrations activates the muscarinic receptors producing depression of MSR. The beneficial action of pretreatment with antimuscarinic agents may be attributed to the protection of the muscarinic receptors.
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thyrotropin releasing hormone induced potentiation of spinal Monosynaptic Reflex in rats in vitro
Indian Journal of Experimental Biology, 1993Co-Authors: Shripad B Deshpande, J E WarnickAbstract:Superfusion of thyrotropin-releasing hormone (TRH) in neonatal rat spinal cord in vitro produced dose (0.01-1.00 microM) dependent potentiation of Monosynaptic Reflex (MSR) which was maximum (44% of control) at 1 microM of TRH. But no ventral root depolarization was observed with TRH (1 microM) although potassium concentration out side ([K+]0) when increased produced a depolarization at the magnitude of 0.2 mV/mM of [K+]0. TRH-induced potentiation of MSR was not altered in spinal cords, obtained from the animals pretreated with 5,7-dihydroxytryptamine or 6-hydroxydopamine. Neither serotonin antagonists (spiperone, ketanserin, cyproheptadine or 3-troponyl-indole-3-carboxylate) nor adrenergic antagonists (phentolamine or haloperidol) could attenuate TRH-induced potentiation. Inhibition of MSR observed in the spinal cord elicited by stimulating the adjacent dorsal root was unaffected by TRH. The results suggest that, TRH potentiates MSR by directly acting on the motoneurons, without involving presynaptic serotonergic or catecholaminergic neuronal systems or the disinhibition of pre- or post-synaptic inhibition in the spinal cord.