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Volume 30, Issue SUPPLEMENT
Displaying 1-10 of 10 articles from this issue
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MUNEYASU SHIROUZU, HIROSHI KIMURA, TOSHIHARU YAMAMOTO, JUNZO OCHI, KAZ ...1983 Volume 30 Issue SUPPLEMENT Pages S1-S9
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSA new type of antibody was successfully produced in rabbits with TRH-BSA as an antigen. The conjugation was based on the amide bond using a carbodiimide coupling method. With this antiserum an enzyme immunoassay (EIA) for TRH was developed, and the neutralization of anti-TRH activity with an excess amount of synthetic TRH was confirmed. Very little or no cross-reaction was observed with TRH-BDB-BSA, an immunogen for generating anti-TRH serum used in previous reports. When the new type of antibodies were used for immunohistochemistry in the mammalian hypothalamus, many neuronal somata with TRH immunoreactivity were visible in animals without colchicine treatment. In addition to the known distribution of TRH cell bodies in the hypothalamus, another cell group was demonstrated to contain TRH immunoreactivity. The anti-TRH serum produced by this method should be useful for investigating extrahypothalamic TRH systems.View full abstractDownload PDF (6871K) -
K. Inanaga, S. Nishi1983 Volume 30 Issue SUPPLEMENT Pages preface1
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSDownload PDF (55K) -
HIROE INOKUCHI, JUN NAKAMURA, SYOGORO NISHI, KAZUTOYO INANAGA1983 Volume 30 Issue SUPPLEMENT Pages S11-S18
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSA TRH analog (DN-1417; γ- butyrolactone -γ- carbonyl - histidylproliamide citrate) with antiepileptic actions altered the electrical activities of hippocampal pyramidal neurons in the guinea-pig brain slice as measured with intracellular recording techniques. DN-1417 hyperpolarized about 20% of the neurons examined. This hyperpolarization was accompanied by an increase in a voltage-dependent potassium conductance. DN-1417 suppressed spontaneous action potentials by depressing spontaneous oscillations of the membrane potential. The oscillations were reduced by DN-1417 through a blockade of tetrodotoxin sensitive non-inactivating Na channels. DN-1417 decreased the amplitudes of EPSPs by a presynaptic depressant action.View full abstractDownload PDF (5907K) -
TADATOSHI HASHIMOTO, NAOHISA FUKUDA, YOSHIAKI SAJI, YUJI NAGAWA1983 Volume 30 Issue SUPPLEMENT Pages S19-S27
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSThe actions of TRH and its analog, γ - butyrolactone - γ -carbonylhistidyl prolinamide citrate (DN-1417) on the unit activities of the cerebral cortex, caudate -putamen and nucleus accumbens were examined using a microelectrophoretic technique in anesthetized rats. Over 80% of the neurons examined in the nucleus accumbens responded to TRH and DN -1417. The effects were mainly inhibitory, but excitatory effects (12-17%) were also detected. In the cerebral cortex and caudate -putamen, only one-third of the neurons were depressed by TRH and DN-1417. DN-1417 exerted an effect similar to TRH on almost all neurons. Dopamine affected almost all neurons. Its main effect was inhibition, but excitation was also observed in some neurons of the nucleus accumbens. Methamphetamine mimicked dopamine in the three regions. However, it was observed that TRH and DN-1417 mimicked dopamine only in the nucleus accumbens neurons. Furthermore, both the inhibitory and excitatory actions of TRH, DN -1417 or dopamine were attenuated by the dopamine receptor antagonist, haloperidol, which was administered systemically. These results suggest that : (1) TRH and DN -1417 have similar actions on the neurons; (2) TRH and DN-1417 act more selectively than dopamine and methamphetamine on the nucleus accumbens neurons, and they may act indirectly on dopaminergic neurons of the nucleus accumbens through an action on presynaptic sites; (3) Endogenous TRH may play a physiological role as a neuromodulator of dopaminergic transmission in the nucleus accumbens.View full abstractDownload PDF (4387K) -
SHIGETO YAMADA, HIDEKI KOJIMA, TETSUYUKI TSUTSUMI, JUN NAKAMURA, SHIGE ...1983 Volume 30 Issue SUPPLEMENT Pages S29-S35
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSEndogenous dopamine (DA) released from slices of rat striatum and n. accumbens into the superfusate was quantified with high performance liquid chromatography (HPLC) combined with an electrohemical detector (ECD). The basal efflux of DA from slices of rat striatum and n. accumbens were 600 pg/mg protein/10 min and 400 pg/mg protein/10 min, respectively. Compared with normal K+ Krebs-Ringer solution, 25 mM K+ Krebs-Ringer solution significantly incleased (about 20 times) the DA efflux. This stimulant effect of high K+ did not occur in Ca2+ deficient Krebs - Ringer solution. Methamphetamine (10-7 -10-3M) caused significant increases in DA efflux in a dose dependent manner. This system may be quite useful to investigate endogenous DA releasing mechanisms in slices of rat brain. Thyrotropin releasing hormone (10-5 -10-3M) did not increase the DA release from either the n. accumbens or the striatum. On the other hand, DN -1417, γ-butyrolactone-γ-histidyl-prolinamide citrate, caused a significant increase in DA efflux from both regions. Removal of Ca2+ from the Krebs-Ringer solution abolished the effect of DN-1417. The stimulant effect of DN -1417 seemed to be greater in the n. accumbens than in the striatum.View full abstractDownload PDF (3116K) -
HIDEYASU YOKOO, TATSUO NAKAHARA, HIDEYUKI UCHIMURA, TAKASHI MATSUMOTO, ...1983 Volume 30 Issue SUPPLEMENT Pages S37-S43
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSTyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis was assayed in 12 regions of rat brain following chronic treatment with DN -1417 (γ-butyrolactone-γ-carbonyl-histidyl-prolinamide), a synthetic TRH analog. Chronic DN-1417 treatment (20 mg/kg i. p., 7 daily injections) increased the TH activity in the ventral tegmental area, nucleus arcuatus and nucleus locus coeruleus, and decreased the TH activity in the frontal cortices, olfactory tuberculum and nucleus paraventricularis. No significant change in TH activity was observed in the nucleus accumbens, nucleus caudatus putamen, median eminence and substantia nigra. These results suggest that DN -1417 exerts some of its effects through dopaminergic neurons, as well as noradrenergic neurons; and the mesolimbic and mesocortical dopamine system may be intimately involved in the central actions of DN-1417.View full abstractDownload PDF (2074K) -
Relationship to their central actionsKUNIHIKO FUNATSU, SHIGEKI TESHIMA, KAZUTOYO INANAGA1983 Volume 30 Issue SUPPLEMENT Pages S45-S50
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSThere are at least two types of [3H]TRH binding sites in the rat brain. High-affinity sites are regulated by GTP in an inhibitory manner. TRH, MK-771 and DN-1417 have high affinities for the high-affinity sites. MK-771 and DN-1417 have, however, much less affinity than TRH at the low-affinity binding sites. As MK-771 and DN-1417 are more potent in central activities and equipotent (MK-771) or less potent (DN-1417) in neuroendocrine activities, it was suggested that the high-affinity [3H]TRH binding sites are the putative TRH receptors which mediate the central actions. The low-affinity [3H]TRH binding sites have characteristics similar to the pituitary TRH receptors. High-affinity sites were not seen in [3H]-(methyl-histidyl)-TRH ([3H] MeTRH) binding experiments. MeTRH has potent neuroendocrine activity, unlike MK-771 and DN-1417. It is possible that [3H]MeTRH labels only the pituitary-type TRH receptors, but not the receptors which are involeved in the central actions of TRH.Durch die Bindungsstudien zeigten sich zwei Typen der [3H]TRH-Bindungsstellen im Rattengehirn. Der eine zeigte eine höhere Affinität als der andere, und wurde durch GTP hemmend reguliert. TRH, MK-771 and DN-1417, die künstliche Analoga des TRH, hatten eine gleich hohe Affinität an den hoch-affinen Bindungsstellen, jedoch waren MK-771 und DN-1417 viel weniger-affinitiv als TRH an den schwach-affinen Bindungsstellen. Da MK-771 und DN-1417 stärkere Zentralwirkungen und schwächere Neuro-endokrinwirkungen als TRH besitzen, wurde angenommen, dass die hoch-affinen [3H]TRH-Bindungsstellen die putativen TRH-Rezeptoren sind, die ihre Zentralwirkungen vermitteln, and dass die schwach-affinen [3H]TRH-Bindungsstellen eine Bindeeigenschaft besitzten, die den hypophysischen TRH-Rezeptoren ähnlich ist. Die hoch-affinen Bindungsstellen waren nicht im [3H]-(methyl-histidyl) -TRH ([3H]MeTRH) Bindungsexperiment nachweisbar. Dass das MeTRH eine starke Neuroendokrin-Aktivität hat, ist eine gegenteilige Wirkeigenschaft des MK-771 und des DN-1417. Es kann deswegen vernünftig sein anzunehmen, dass [3H]MeTRH nur die Hypophyse-ähnlichen TRH-Rezeptoren im Gehirn labelliert, aber nicht die Rezeptoren labelliert, die die Zentralwirkungen vermitteln.View full abstractDownload PDF (3068K) -
NORIO OGAWA1983 Volume 30 Issue SUPPLEMENT Pages S51-S56
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSProperties of TRH-receptors in the rat central nervous system (CNS) were studied. MK-771 (L-gyro-2-aminoadipyl-histidyl-thiazolidine-4-car-boxamide) and DN-1417 (γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate), potent TRH analogs, had relative potencies of 170% and 30%, respectively, of TRH in the radioreceptor assay. Most of the other TRH analogs which were tested had little potency in reducing the receptor binding of [3H]TRH, indicating that the tertiary structure of the TRH molecule is necessary for binding to the brain receptor. The receptor activity was sensitive to digestion by trypsin or phospholipase A, suggesting that protein and phospholipid moieties are essential for the binding of [3H]TRH. Thiol reagents reduced the binding activity of the receptor, suggesting that an intrcahain disulfide bond may be an important constituent of the binding site for TRH. A therapeutic serum level of Li+ (1 mM) decreased the binding of [3H]TRH, and physiological serum concentrations (20μM) of Cu2+, Zn2+ and Pe2+ increased TRH binding. This indicates that the metal ions had primary significance in the function of CNS TRH-receptors.View full abstractDownload PDF (3484K) -
MITSUMOTO SATO, KIYOSHI MORIMOTO1983 Volume 30 Issue SUPPLEMENT Pages S57-S64
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSAntiepileptic effects of both TRH tartrate (TRH-T) and its derivative, γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate (DN-4417) have been evaluated using the amygdaloid kindling cat preparation. The results reported are: 1) transient anticonvulsant effects unrelated to dose for both TRH-T and DN-1417, 2) long-term elevation of the final electroconvulsive threshold in some cats after TRH-T and DN-1417 treatment, 3) prophylactic effects on kindling seizure development as well as effects to prevent positive transfer of the kindling to the contralateral amygdala after daily treatment with DN-1417, 4) a shortened postictal behavioral depression and EEG silence with DN-1417 and 5) a prolonged postictal seizure inhibition period with DN-1417. It is hypothesized that endogenous TRH inhibits seizure activity and reduces the establishment of epileptogenesis in the brain.View full abstractDownload PDF (4091K) -
JUN NAKAMURA, NAOHISA UCHIMURA, SHIGETO YAMADA, TETSUYUKI TSUTSUMI, KE ...1983 Volume 30 Issue SUPPLEMENT Pages S65-S72
Published: March 31, 1984
Released on J-STAGE: February 08, 2010
JOURNAL FREE ACCESSCannulas were chronically implanted in the ventriculus lateralis of rats. The anticonvulsant effects of DN-1417 (γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate) and TRH-T (pyroglutamyl-histidyl-prolinamide tartrate) were analyzed by observing the changes in convulsive threshold to electrical stimulation. Both DN-1417 and TRH-T had no significant effect on the electroconvulsive threshold. DN-1417 had an anticonvulsant effcet in animals pretreated with α-methylparatyrosine (α-MT). When rats were pretreated with FLA-63, a dopamine-β-hydroxylase inhibitor, the convulsive threshold was only slightly different from the control threshold, therefore, the decrease in the convulsive threshold by α-MT must be due primarily to a decrease in dopamine (DA) content. Changes in the DA content of the striatum also suggested that the anticonvulsant effect of DN-1417 was due to its DA releasing action. Furthermore, the anticonvulsant effect of DN-1417 seemed to have no relationship to the inhibitory activity of GABA.View full abstractDownload PDF (3250K)
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