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Biomedical subjects

Y Nagawa

Publications and source records attributed to Y Nagawa.

At least 55 records · Page 3Linked to original sources
PubMed1982

TRH and its novel analog (DN-1417): antipentobarbital action and involvement of cholinergic mechanisms.

Possible neuroanatomical loci and the mode of action of thyrotropin-releasing hormone (TRH) or its analog, gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate (DN-1417), in reducing the pentobarbital-induced sleeping time were investigated by using an intracerebral microinjection technique in rats. Intravenous, intraperitoneal or intracerebroventricular (ICV) injection of TRH or DN-1417 produced a dose-related reduction of the sleeping time induced by pentobarbital. TRH or DN-1417 given into the posterior hypothalamic regions including the dorsal premammillary nucleus, lateral hypothalamic area and posterior nucleus of hypothalamus had a significant pentobarbital sleep shortening action in low doses. Injection of these peptides into the dorsomedial nucleus of thalamus, mesencephalic reticular formation, medial septal nucleus or hippocampus was also effective, in comparatively low doses. However, higher doses were required to elicit the effect when the injections were made into the nucleus accumbens, lateral preoptic area or caudate nucleus. In this respect, the parietal cortex was insensitive to TRH or DN-1417. The pentobarbital sleep shortening action of TRH or DN-1417 injected peripherally or into the hypothalamic regions was markedly antagonized by ICV or intrahypothalamic pretreatment with atropine methyl bromide. On the contrary, ICV injection of atropine methyl bromide had a weak or no antagonizing action on the effect of TRH injected ICV or into the reticular formation, medial septal nucleus or hippocampus. These results suggest that possible neuroanatomical sites mediating the pentobarbital sleep shortening action of TRH or DN-1417 may be posterior hypothalamic regions, dorsomedial nucleus of thalamus, reticular formation, medial septal nucleus or hippocampus. A cholinergic mechanism may also be involved in the effect of TRH on the hypothalamus.

Animals↗
PubMed1982

Relationship between receptor-binding affinities and TSH-releasing activities of novel TRH analogs in the rat.

Specific bindings of 3H-TRH to rat pituitary homogenate and apparent affinities of TRH analogs for binding sites were studied. The dissociation constant for 3H-TRH binding to rat pituitary homogenate was 30 nM at 0 degrees C, and the number of the binding sites was 120 fmoles/mg protein. The apparent affinities of TRH analogs for the binding sites, which were estimated from the ability to displace 3H-TRH from those binding sites, were found to correlate well with their TSH releasing activities. These findings support the idea that the TSH releasing activities of TRH analogs depend almost entirely upon their binding abilities to the TRH receptor in the pituitary.

Animals↗
PubMed1980

Effect of thyrotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy[14C]glucose method, in conscious and pentobarbitalized rats.

Effects of TRH and pentobarbital alone, and in combination, on local cerebral glucose utilization of rats were studied by the autoradiographic 2-deoxy[14C]glucose method. TRH (5 mg/kg i.v.) reduced the rate of cerebral glucose utilization slightly in the whole brain. Locally, significant depression was observed in the following structures: frontal and visual cortices, hippocampus Ammon's horn and dentate gyrus, medial and lateral geniculate bodies, nucleus accumbens, caudate-putamen, substantia nigra, pontine gray matter, superior colliculus, superior olivary nucleus, vestibular nucleus, lateral lemniscus and cerebellar cortex. Pentobarbital (30 mg/kg i.v.) produced a marked and diffuse reduction in the rate of glucose utilization throughout the brain. TRH given 15 min after the administration of pentobarbital markedly shortened the pentobarbital sleeping time and caused some reversal of the depression in local cerebral glucose utilization produced by pentobarbital. These effects were almost completely abolished by pretreatment with intracerebroventricular injection of atropine methyl bromide (20 microgram/rat). These results indicate that although TRH acts to cause a reduction in the rate of cerebral glucose utilization, it reverses the depression induced by pentobarbital, via a cholinergic mechanism, in a number of structures, some of which are related to monoaminergic systems and the reticulo-thalamo-cortical activating system.

Animals↗
PubMed1980

Blood level and brain distribution of thyrotropin-releasing hormone (TRH) determined by radioimmunoassay after intravenous administration in rats.

The blood level and brain distribution of immunoreactive TRH after intravenous administration of TRH tartrate monohydrate (TRH-T) were investigated by radioimmunoassay in rats. Optimal condition for complete inactivation of TRH-degradative enzymes in brain by a microwave irradiation was found to be a 5kW power for 1.5 seconds. The endogenous TRH was present at the highest concentration in the hypothalamus, followed by the brain stem and thalamus, and was the lowest in the cerebral cortex including hippocampus and cerebellum. The time-course of TRH blood levels following administration of TRH-T at 0.5, 5 and 25 mg/kg fitted to a two compartment open model, and the half-lives in beta-phase increased dose-dependently. The administered TRH was incorporated rapidly from blood into whole brain, and the peak brain level corresponding to 0.108--0.166% of the total dose administered was attained 1 min after the administration. The brain TRH was eliminated with a half-life of about 3 min. The administered TRH was distributed throughout the brain, at the highest concentration in the hypothalamus, followed by the brain stem, cerebellum, thalamus and cerebral cortex. TRH tended to be eliminated most rapidly from the cerebellum.

Animals↗
PubMed1980

[Behavioral changes following lesioning of the nucleus accumbens (ACB) and effects of centrally acting drugs in rats (author's transl)].

ACB is one of the sites containing nerve terminals of the mesolimbic dopamine system. We have found that all the male Sprague-Dawley rats with electrolytic lesions of bilateral ACB showed locomotor hyperactivity and hyperemotionality. Muricide was also observed in about 40% of these lesioned rats. Hyperemotionality and muricide were maximum during the first 2-3 days after the lesioning, then gradually declined. Locomotor hyperactivity lasted invariably for over 30 days. Hyperemotionality and muricide were both inhibited by the following drugs given i.p., chlorpromazine; haloperidol; diazepam; estazolam; aminooxyacetic acid (GABA transaminase inhibitor); phenoxybenzamine. However, imipramine, atropine and L-5-hydroxytryptophan inhibited selectively the muricidal behavior. Lesioning of the catecholaminergic (CA) system by administration of 6-hydroxydopamine into bilateral ACB-produced only moderate hyperemotionality with no evidence of locomotor hyperactivity and muricide. These results suggest that lesioning of the CA system plus other neural mechanisms in ACB are required for development of these three forms off hyperemotional behavior. Cholinergic, serotonergic, GABAergic and CA mechanisms may also be involved in hyperemotionality and muricide in ACB lesioned rats.

5-Hydroxytryptophan↗
PubMed1980

[A procedure for recording electroretinogram (ERG) in conscious monkeys, and effects of some drugs (author's transl)].

Stable ERG was successfully recorded using a contact lens-type electrode in conscious cynomolgus monkeys restrained in a monkey-chair with a specially devised head-holder. After adaptation to darkness, single photostimulation evoked ERG consisting of an initial negative wave (a-wave), followed by a positive wave superimposed with oscillatory potentials (b-wave), and a late positive (c-wave). The former two waves were clearly recorded but c-wave was often mixed with artifacts probably due to eye movements. Amplitudes and peak latencies of a- and b-waves increased in progression of dark adaptation and attained to maximum within 20 min. The optimal intensity of photostimulus and time-constant for recording stable a- and b-waves with intermediate amplitudes were found to be 2 joule and 0.1 sec, respectively. The amplitudes and peak latencies (mean +/- s.d.) of a- and b-waves obtained by these conditions were 163.3 +/- 44.9 and 437.0 +/-37.9 microV, and 17.3 +/- 0.5 and 53.5 +/- 3.2 msec, respectively. These waves were reproducible within 25% variations change in a-wave: pentobarbital increased the amplitude of b-wave, whereas ketamine reduced this amplitude. A 3-day treatment with 1,5-di(p-aminophenoxy)pentane (200 mg/kg/day, p.o.), a retinal toxic and behavioral signs of visual dysfunction. Histological abnormality of the retina was also detected. The results indicate that this technique is useful for recording ERG in order to evaluate the effect of chronically treated drugs on visual perception in conscious monkeys.

Adaptation, Ocular↗
PubMed1979

[Thyrotropin-releasing hormone (TRH): action mechanism of an enhanced dopamine release from rat striatal slices (author's transl)].

The enhancing effect of TRH on dopamine(DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10(-5)--10(-3) M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10(-6)--10(-4)M) exhibited a considerable inhibitory effect. TRH (10(-7)--10(--3)M) alone did not increase the DA release into the incubation medium, but it clearly enhanced the DA release in the concomitant presence of desipramine (5 x 10(-5)M). In the superfusion study, TRH (10(-5)--10(-3)M), methamphetamine (10(-6)--10(-4)M) and KCl (2.5--5.0 x 10(-2)M) enhanced the DA release into the perfusion fluid. The DA releasing effect of TRH was completely blocked by cholinergic blockers (scopolamine, hexamethonium and hemicholinium), Ca2+ chelator(EGTA), Ca2+ antagonist(CoCl2) and Ca2+ influx blocker(D-600) or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release, however, was not modified by the above treatments except for a partial decline produced by EGTA coupled with the removal of Ca2+. TRH(10(-4)M) also facilitated the uptake of norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-(6)--10(-4)M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10(-5)--10(-4)M) and methamphetamine (10(-7)--10(-4)M) enhanced the NE release into the perfusion fluid. Therefore, it can be concluded that TRH facilitated the DA release from rat striatal slices by mediating through a cholinergic mechanism and enhancing the influx of Ca2+.

Amino Acids↗
PubMed1979

[Thyrotropin-releasing hormone (TRH): Enhancement of dopamine dependent circling behavior and its own circling-inducing effect in unilateral striatal lesioned animals (author's transl)].

Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals.

Animals↗
PubMed1979

[Behavioral and EEG alterations with brain stem compression and effect of thyrotropin-releasing hormone (TRH) in chronic cats (author's transl)].

Behavioral and EEG changes induced by brain stem compression and the effect of TRH were studied. The compression was given for 1 to 6 min by inflating a balloon chronically implanted on the dorsal surface of the cat brain stem in the 4th ventricle via cisterna magna. Within 10 to 36 sec after the start of the compression, the cats turned sideways and became motionless in a spastic extension of four legs, and thereafter all reverted to a normal position, after 45 to 120 min, although slight movements or head-up position was observed in some animals. The cortical EEG patterns observed after the compression were initially a brief rush of low amplitude-fast waves (EEG arousal) followed by a flattened and/or spike pattern, and subsequently these shifted to high amplitude-slow waves with or without an accompanying EEG arousal. These behavioral EEG alterations were remarkably improved by i.v. administration of TRH as follows: eight of 12 cats with 1 mg/kg and one of 4 cats with 0.5 mg/kg promptly changed from the lateral to a crouching or abdominal position, and thereafter never turned sideways again. Partial recovery such as movements of forelegs, struggling or head-up in the lateral position, rolling or slight shift of position was also observed within several min in three cats with 1 mg/kg as well as in two cats with 0.5 mg/kg. Furthermore, TRH induced a dose dependent, persistent EEG arousal in all cats. These results show that TRH ameliorates deterioration in behavior and the EEG, this deterioration being similar to clinical states of disturbance in consciousness induced by compressing the brain stem.

Animals↗
PubMed1979

Thyrotropin-releasing hormone: hyperactivity and mesolimbic dopamine system in rats.

The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 micrograms into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by alpha-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine O-sulphate (100 micrograms) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 micrograms) given intraperitoneally or into the NAS. Both TRH (10(-5) and 10(-4) M) and methamphetamine (10(-6)--10(-4) M increased the spontaneous release of 14C-DA from rat NAS slices. These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA recptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system.

Animals↗
PubMed1979

Effects of vasopressin and cyclic AMP on water transport at arachnoid villi of cats.

The effects of vasopressin and cyclic AMP on water transport at arachnoid villi into the superior sagittal sinus were examined using the isolated meninges preparations of cats. The meninges preparation, the superior sagittal sinus of which was opened at the midline of the outer surface, was held between two polyethylene tubes. The tubes were fixed vertically in the way that the opened surface of the sinus was directed downward and arachnoid surface upward. Water transport was determined by measuring the tritiated water dripping through the membrane preparation. Vasopressin from less than 50 to 500 muU/ml accelerated the water transport and this effect was dose-dependent. Cyclic AMP from 0.5 to 10 mM was proved to manifest the same effect as vasopressin. This effect of cyclic AMP appeared rapidly in comparison with that of vasopressin, suggesting that the effect of vasopressin may be manifested through cyclic AMP. From these findings a physiological role of vasopressin in cerebrospinal fluid was discussed regarding the regulation of intracranial pressure.

Animals↗
PubMed1978

Effect of vasopressin on intracranial pressure of rabbit.

Effect of vasopressin on intracranial pressure (ICP) was examined by an intraventricular administration of the hormone to a rabbit. ICP was determined at the cisterna magna with a manometer and recorded automatically with a recorder. An injection of over 150 micro U of vasopressin lowered ICP, but there was no clear dose-response relationship of the effect of vasopressin on ICP. When vasopressin was injected intraventricularly after lowering ICP by an intravenous injection of acetazolamide which inhibits the production of cerebrospinal fluid (CSF), an additive effect of the hormone on ICP was observed. The effect of vasopressin on excretion of water in CSF was examined by the determination of drainage of tritiated water injected into the lateral ventricle of a rabbit. Drainage of radioactive water into vein was measured by collection of blood at the internal jugular vein and radioactivity of the plasma was counted. Vasopressin accelerated excretion of tritiated water into vein. These results indicate that vasopressin facilitated drainage of CSF into vein to lower ICP.

Acetazolamide↗
PubMed1977

Mesolimbic involvement in the locomotor stimulant action of thyrotropin-releasing hormone (TRH) in rats.

Thyrotropin-releasing hormone (TRH) injected i.p. in doses of 5 mg/kg and higher had a strong locomotor stimulant action with development of frequent rearing, mild sniffing, grooming, preening and other excitatory behaviours. The locomotor stimulation was also produced by bilateral injection of TRH and dopamine (DA) into the nucleus accumbens but not by bilateral injection of these substances into the caudate nucleus. Unilateral intracaudate injection of TRH provoked no behavioural changes in contrast to a distinct circling response to similarly injected DA. Either i.p. or bilateral intra-accumbens injection of haloperidol or pimozide on low doses effectively blocked the locomotor stimulant action of TRH. These results indicate that the DA system in the nucleus accumbens may be of importance in mediation of the locomotor stimulant action of TRH. Differential affinity of TRH to the two DA systems, the mesolimbic and nigrostriatal DA systems is also suggested.

Animals↗