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K Otake

Publications and source records attributed to K Otake.

At least 73 records · Page 4Linked to original sources

Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular (i.c.v.) administration of PACAP raised the plasma AVP concentration in a dose-dependent manner (50-500 pmol/rat), and the maximum effect was obtained at 5 min after the administration. This AVP-releasing effect was not due to a fall of blood pressure, increase of plasma Na or decrease of plasma volume, all of which are known to stimulate AVP release. PACAP had little effect on blood pressure at a low dose, but at higher doses increased it. Vasoactive intestinal peptide (VIP), which is homologous to PACAP, also raised the plasma AVP concentration by i.c.v. injection. An antagonist for VIP receptor, [Lys, Pro, Arg, Tyr]-VIP inhibited the VIP-induced increase of plasma AVP, but had little effect on PACAP-induced increase of plasma AVP. These results suggest that PACAP stimulates AVP release, via specific receptors which are distinct from VIP receptors.

Animals↗

Projections from the commissural subnucleus of the nucleus of the solitary tract: an anterograde tracing study in the cat.

The commissural subnucleus (COM) of the nucleus of the solitary tract (NTS) is known to receive primary afferents from the lungs and other viscera innervated by the vagus nerve, and thus to participate in central autonomic and respiratory control. The aim of the present study was to identify the areas of terminal arborizations of COM neurons in order to examine brainstem sites which may be involved in reflex responses mediated by these neurons. The projections were studied in cats, using biocytin as an anterograde tracer. Labeled fibers and terminal boutons were visualized by horseradish-peroxidase histochemistry, 2-3 days after microinjection of the tracers into the COM 1-2 mm caudal to the obex. Labeled axons were examined in the brainstem from the rostral pons to the caudal medulla and were found bilaterally, with an ipsilateral predominance, mainly in the following regions: (1) The dorsolateral rostral pons. Terminal boutons were observed in the lateral and medial parabrachial nuclei, Kölliker-Fuse nucleus, and around the mesencephalic trigeminal tract. This area corresponds to the pontine respiratory group also known as the "pneumotaxic center." (2) The pontine area dorsolateral to the superior olivary nucleus. This region contains the A5 noradrenergic cell group; (3) Near the ventral surface, below the facial nucleus. This area overlaps with the 'retrotrapezoid nucleus.' (4) Respiration-related areas of the medulla, including the dorsal and ventral respiratory groups, and the Bötzinger complex. (5) The dorsal motor nucleus of the vagus. These results suggest that the COM is involved in reflex arcs, which have both respiratory functions and autonomic functions. The pathway to the dorsolateral pons, which has been identified in our recent electrophysiological study is likely to play a role in mediating respiratory responses from pulmonary rapidly adapting receptors. Other pathways may represent additional projections from second-order neurons receiving input from this group of lung receptors, or projections from as yet unidentified neurons that relay information from different afferents terminating in the COM.

Animals↗

Efferent projections of pulmonary rapidly adapting receptor relay neurons in the cat.

Axonal projections of second order neurons activated by vagal afferent fibers originating from pulmonary rapidly adapting receptors (RARs) were studied electrophysiologically in Nembutal-anesthetized, paralyzed and artificially ventilated cats. Extracellular recordings from these neurons (referred to as 'RAR-cells') were made in the commissural subnucleus (COM) of the nucleus of the solitary tract (NTS). They were identified by a combination of stimuli including stimulation of the vagus nerve(s), hyperinflation and deflation of the lungs, and a brief period of ammonia vapor inhalation. A total of 80 RAR-cells were tested for axonal projections to a respiration-related area in the brain-stem, either the dorsolateral rostral pons or the dorsal respiratory group (DRG) or the ventral respiratory group (VRG) or the Bötzinger complex (BOT) and/or the spinal cord. Twenty-two of the 47 (47%) RAR-cells tested for ipsilateral pontine projection could be antidromically activated, and in 8 cases evidence for axonal arborization was obtained. Only 1 of the 11 RAR-cells tested for DRG projection, and 1 of the 10 RAR-cells tested for VRG projection, were antidromically activated. No RAR-cells were activated from the BOT (n = 8) or from the C3-C4 segments of the spinal cord (n = 11). Bilateral lesions of the COM abolished the reflex responses induced by ammonia inhalation or hyperinflation of the lungs, but not the Hering-Breuer reflex. These results indicate that a pathway from the COM to the rostral pons forms part of the reflex arc originating from RARs.

Animals↗

Centrally administered galanin inhibits osmotically stimulated arginine vasopressin release in conscious rats.

The effect of centrally administered galanin on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of porcine galanin suppressed hypertonic saline-induced increase in plasma AVP in a dose-dependent manner (12.5-100 pmol/rat) at 10 min after the injection. Pretreatment with subcutaneous injection of naloxone (1 mg/100 g b.wt.) partially blocked the galanin-induced effect on plasma AVP. These results suggest that central galanin inhibits osmotically stimulated AVP release and endogenous opioids are, at least in part, involved in the mechanism.

Animals↗

Possible involvement of endogenous opioid peptides in the inhibition of arginine vasopressin release by gamma-aminobutyric acid in conscious rats.

We examined the effects of gamma-aminobutyric acid (GABA) and naloxone, a potent opioid antagonist, on arginine vasopressin (AVP) secretion in conscious rats in order to study the relationship of GABA and endogenous opioid peptides in the regulation of AVP secretion. Intracerebroventricular administration of GABA caused a time- and dose-dependent decrease in the plasma concentration of AVP that was elevated by hypertonic saline injection, whereas it did not affect the basal AVP. Pretreatment with naloxone (10 mg/kg) significantly attenuated the inhibitory effect of GABA (100 micrograms) on AVP release. These results suggest that GABA produces an inhibition of AVP release stimulated by hypertonic saline, and that this inhibitory effect may be mediated at least in part by the endogenous opioid systems.

Animals↗

Prolactin secretion in patients with idiopathic diabetes insipidus.

It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.

Adolescent↗

[Clinical assessment of posterior pituitary function by measurement of unextracted random urine].

To evaluate posterior pituitary function without any provocative examination, vasopressin (AVP) concentrations of random urine were measured by high-sensitive radioimmunoassay (AVP-RIA Kit, Mitsubishi Petrochemical Co., Ltd.). No apparent interference for the AVP measurement in unextracted urine was seen after appropriate dilution of urine sample. Urinary AVP did not degenerate at least for 24 hr at room temperature. AVP concentration of random urine was significantly correlated with AVP excretion in 24hr-urine in normal subjects. In 25 patients with neurogenic diabetes insipidus diagnosed by hypertonic saline infusion test, the AVP concentration in random urine was less than 13 pg/mg Cr. In approximately 1% of the normal subjects the urinary AVP level was below this range. Therefore, more intensive examinations should be planned to rule out the failure of AVP secretion in the case of such low AVP level in random urine. We also investigated the physiological changes in AVP secretion in 815 children and 352 pregnant women by measurement of urinary AVP. Even a large number of samples could be measured using this simple procedure.

Adolescent↗

Medullary projection of nonaugmenting inspiratory neurons of the ventrolateral medulla in the cat.

In Nembutal-anesthetized, immobilized, and artificially ventilated cats, we studied the morphological characteristics of inspiratory neurons with nonaugmenting firing patterns. HRP was injected intracellularly into a total of 22 neurons of the Bötzinger complex (BOT) and the ventral respiratory group (VRG). In 20 cases somata with their axonal trajectories were stained, and in two cases only axons were stained. None of the neurons stained could be antidromically activated by stimulation of the cervical cord. The somata of 20 neurons were located in the vicinity of the nucleus ambiguus or the retrofacial nucleus (RFN) between 600 microns and 2,800 microns caudal to the rostral end of the RFN. Their axons could be traced for a distance of several millimeters on the side of the somata, and showed various projection patterns. According to these projection patterns, the 20 neurons were tentatively classified into four groups: A (8/20), B (4/20), C (6/20), and motoneurons (2/20). Group A neurons gave off extensive axon collaterals that arborized and distributed boutons predominantly in the BOT and the VRG areas. Group B neurons had less extensive axon collaterals with various projection patterns, projecting rarely to the BOT or the VRG area. Group C neurons sent their stem axons, without issuing any axonal collaterals, to the contralateral side in five cases and to the ipsilateral pons in one case. The two motoneurons had axons leaving the brainstem without any intramedullary collaterals. Thus, the nonaugmenting inspiratory neurons showed morphological variations, which may play different roles in neural control of respiration.

Animals↗

Excitation and inhibition of medullary inspiratory neurons by two types of burst inspiratory neurons in the cat.

In Nembutal-anesthetized and artificially ventilated cats, we studied the connectivity of burst inspiratory (I) neurons in the Bötzinger complex and the ventral respiratory group (VRG) with spike-triggered averaging methods. Burst I neurons exhibited tonic (I-TON) or decrementing (I-DEC) firing patterns. Spikes of I-TON neurons induced monosynaptic EPSPs in intracellularly recorded I neurons of both the VRG and the dorsal respiratory group (DRG). Spikes of I-DEC neurons induced monosynaptic inhibitory postsynaptic potentials (IPSPs) in both VRG and DRG I neurons.

Action Potentials↗

Axonal trajectory and terminal distribution of inspiratory neurons of the dorsal respiratory group in the cat's medulla.

In Nembutal-anesthetized and artificially ventilated cats, we studied the morphological properties of the inspiratory neurons of the dorsal respiratory group (DRG) with HRP intracellular staining. A total of 37 neurons were stained and their axonal trajectories and terminal distribution in the medulla were analyzed. The somata were located predominantly in the ventrolateral region of the nucleus of the solitary tract and were distributed between 2,300 mum rostral and 700 mum caudal to the obex. Most (26/33) of the neurons tested were antidromically activated by the stimulation of the contralateral (n = 24) or ipsilateral (n = 2) cervical cord. To examine the existence of collateral branches in the brainstem, we traced axonal trajectories in 28 neurons. In most cases, the stem axons issuing from the cells of origin coursed ventrally and then turned medially to cross the midline without giving off any axon collaterals. However, six neurons had axonal collaterals in the brain stem ipsilateral to the somata. At least four types of collateralization were observed. The stem axon of the first type bifurcated at the area ipsilateral and ventral to the cell body. One branch crossed the midline to project to the spinal cord, and the other, thinner branch descended caudally in the ipsilateral medullary reticular formation without distributing any terminals. The axon of the second type projected to the contralateral spinal cord and distributed collateral branches with terminal boutons in the ipsilateral ventral respiratory group (VRG). The third type projected to the contralateral spinal cord and distributed terminal boutons in the medial part of the nucleus of the solitary tract (NTS) and its vicinity. The fourth type distributed numerous branches with terminal boutons in and around the ventral part of the NTS and the VRG area. This study indicates that some inspiratory neurons of the DRG influence not only spinal respiratory neurons but also medullary respiratory neurons in the vicinity of the DRG and the VRG.

Animals↗

[Radioimmunoassay of vasopressin in unextracted random urine; clinical application for screening of central diabetes insipidus].

The concentration of unextracted urinary arginine vasopressin (UAVP) was directly measured by high-sensitive radioimmunoassay (AVP-RIA Kit, Mitsubishi Petrochemical Co., Ltd.). Urine was diluted to eliminate interference of nonspecific substance without prior extraction. When urine aliquots were diluted in 4 to 32 fold in assay buffer, the relationship between UAVP concentration and dilution ratio corresponded exactly in a linear regression line. The elution pattern on Sephadex G-25 of UAVP immunoreactivity was identical with that of synthesized AVP. The AVP concentration in unextracted urine was not significantly different from that of extracted urine by Sep-Pak C18 column (Water Associates, Milford MA). The mean recovery of added AVP to urine specimens was 101.1 +/- 9.8% (mean +/- SD). The immunoreactivity of UAVP was not modified by either albuminuria (50 and 100 mg/dl) or glycosuria (1000 g/dl). Mean coefficients of variance between-assay and within-assay were 8.3% and 6.6% respectively. In normal subjects (n = 28), significant correlation was observed between UAVP concentration and simultaneously measured plasma AVP (r = 0.701, p less than 0.001). Moreover, AVP concentration in random urine was significantly correlated with AVP excretion in 24 hr-urine (r = 0.703, p less than 0.05, n = 9), and this suggested that random UAVP concentration may indicate daily UAVP secretion. In normal subjects, AVP concentration in random urine was widely scattered from 9.2 to 470.6 pg/mg Cr (89.5 +/- 76.4 pg/mg Cr, n = 211). In patients with diabetes insipidus (DI), UAVP concentration (1.6 to 13.0 pg/mg Cr, 6.94 +/- 2.77 pg/mg Cr, n = 25) was significantly lower (p less than 0.001) than that of normal subjects. UAVP concentration in a patient with primary polydipsia (43.2 pg/mg Cr) was not similar to that of ID but to that of normal subjects. UAVP concentration in 2 patients with SIADH was not more than that of normal subjects, indicating that random UAVP concentration is not suitable for detecting inappropriate AVP secretion. In this study, it is suggested that patients of random UAVP concentration below 13.0 pg/mg Cr should be recommended other intensive examination to diagnose DI, even though 2 normal subjects (0.9%) were incorrectly estimated as DI. In conclusion, radioimmunoassay of AVP in unextracted random urine is easy to sample and assay, and useful in screening polyuric patients.

Diabetes Insipidus↗

Morphology of augmenting inspiratory neurons of the ventral respiratory group in the cat.

The present study examined, in Nembutal-anesthetized and artificially ventilated cats, the morphologic properties of the inspiratory neurons of the ventral respiratory group (VRG). Horseradish peroxidase (HRP) was injected into 21 augmenting inspiratory or late inspiratory neurons with peak firing rates in the late inspiratory phase. The majority of the stained neurons were antidromically activated by stimulation of the cervical cord. Thirteen somata, located within or around the nucleus ambiguus (AMB), between 100 microns caudally and 2,000 microns rostrally to the obex, were stained. In ten cases, the stem axons issuing from the cells of origin coursed medially to cross the midline without giving off any axonal collaterals. Three neurons gave rise to axonal collaterals on the ipsilateral side, distributing boutons in the medullary reticular formation, in the vicinity of the AMB, hypoglossal nucleus, solitary tract, and dorsal motor nucleus of the vagus. In eight neurons, only the axons were labeled; in four of these, which were antidromically activated from the spinal cord, the stem axons crossed the midline 2,000-3,000 microns rostral to the obex and descended in the reticular formation around the AMB down to the cervical cord. They issued several axonal collaterals, distributing terminal boutons at the level of the caudal end of the retrofacial nucleus and about 1,000 microns rostral and caudal from the obex. Terminals were found mainly in and around the AMB, and a few were found in the vicinity of the dorsal motor nucleus of the vagus. The remaining four nonactivated axons distributed their terminal boutons widely in the reticular formation around the AMB. Thus, the augmenting inspiratory neurons of the VRG were shown to project not only to the spinal cord, but also to the VRG, hypoglossal nucleus, and dorsal motor nucleus of the vagus.

Action Potentials↗

Axonal projections from Bötzinger expiratory neurons to contralateral ventral and dorsal respiratory groups in the cat.

We studied projection patterns of the augmenting expiratory neurons of the Bötzinger complex (BOT) in the contralateral brainstem. Three experimental approaches were used: 1) electrophysiological analysis using antidromic microstimulation, and morphological analyses using 2) intraaxonal injection of HRP, and 3) application of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). Taken together, the three methods revealed morphological details of the axonal arborizations of the expiratory neurons in the BOT and the ventral respiratory group (VRG). The majority of augmenting expiratory neurons of the BOT had axonal collaterals in the contralateral brainstem. The stem axons to the contralateral side crossed the midline almost at the level of the cell somata. They descended dorsomedial to the ventral spinocerebellar tract and gave off collateral branches directed dorsomedially. Terminal boutons were distributed abundantly in the caudal part of the BOT and in the more caudally situated VRG. Axon collaterals sometimes ran to the dorsal respiratory group (DRG) and distributed terminal boutons there. Together with the fact of extensive ipsilateral arborizations shown previously, the present results indicate that the augmenting expiratory neurons of the BOT have wide bilateral influence on the BOT, VRG, DRG, and spinal cord.

Animals↗

Morphology of expiratory neurons of the Bötzinger complex: an HRP study in the cat.

In anesthetized and artificially ventilated cats, the physiological and morphological properties of expiratory neurons or their axons of the Bötzinger complex (BOT) were studied using intracellular recording and intracellular HRP labeling techniques. Thirteen expiratory neurons (nine cell somata and four axons) were successfully stained. Four of them were motoneurons, having relatively large cell somata in the retrofacial nucleus (RFN) and axons without any collaterals inside the brainstem. All the motoneurons showed a plateau shape of depolarization potentials during the expiratory phase. Any of the other nine expiratory neurons exhibited augmenting type firing or membrane potential changes during the expiratory phase. In five out of nine augmenting neurons, cell somata were stained and located ventral to the RFN. In four, only axons were stained. The majority of the augmenting neurons had two major axonal branches: one traveling toward the contralateral side and the other descending ipsilaterally in the brainstem. The most striking feature of the axonal trajectory was that all of the stained augmenting expiratory neurons, including the axons, had collateral branches with synaptic boutons in the BOT area, thus indicating that BOT expiratory neurons interact with some respiratory neurons in the BOT area and its vicinity.

Animals↗

Regional lymph node metastasis in carcinoma of the hamster tongue.

The incidence of regional lymph node metastasis in the hamster tongue carcinoma induced by DMBA was studied. Metastasis to the regional lymph node was confirmed by histologic examination in 25 (22.1%) of the 113 experimental animals. Of a total of 238 lymph nodes examined, metastatic deposits were found in 35 (14.6%) lymph nodes. Systemic administration of cortisone increased the rate of metastasis from 16.7% to 26.1%, but the difference was not statistically significant. The necessity of extending the tumor-bearing period and the addition of mechanical trauma to the primary carcinoma to increase the rate of metastasis are stressed.

9,10-Dimethyl-1,2-benzanthracene↗