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H Koda

Publications and source records attributed to H Koda.

At least 37 records · Page 2Linked to original sources
PubMed1994

Forskolin does not augment the bradykinin response of canine visceral polymodal receptors in vitro.

In clarifying the possible involvement of cyclic AMP (cAMP) in prostaglandin (PG) E2-induced sensitization of the bradykinin response of canine testicular polymodal receptors, the effects of forskolin, an activator of adenylyl cyclase, were studied in the presence and absence of acetylsalicylic acid (ASA, 550 microM) which blocks PG production. Forskolin (10 microM) seldom induced discharges in polymodal receptors. An unexpected outcome of this study was that forskolin induced no facilitation of the bradykinin (0.1 microM) response, both in the absence and presence of ASA. A slight yet significant suppression of the bradykinin response was instead observed in the absence of ASA. These results suggest that intracellular cAMP may be related with PG E2-induced sensitization of the bradykinin response through its decrease.

Adenylyl Cyclases↗
PubMed1993

Involvement of EP3 subtype of prostaglandin E receptors in PGE2-induced enhancement of the bradykinin response of nociceptors.

Prostaglandin E2 augments bradykinin-induced discharges of polymodal receptors as studied in vitro preparations. The antagonist and agonists for three subtypes of EP receptors were used to determine which subtype is involved in this phenomenon. The agonist for EP3 (M&B28767) simulated the PGE2-induced effect but not for EP2 (butaprost). The antagonist for EP1 (AH6809) did not suppress the effect. These findings indicate the involvement of the EP3 receptor subtype in the effect.

Alprostadil↗
PubMed1993

Augmenting effects of cyclic AMP on the heat response of canine testicular polymodal receptors.

It has long been thought that the augmenting effects of E series prostaglandins (PG) are mediated by cyclic AMP (cAMP). In clarifying the validity of this hypothesis, we studied the effects of increases in intracellular cAMP on the heat response of testicular polymodal receptors. Recordings were obtained from testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Induction of increases in intracellular cAMP by either forskolin, an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (10(-4) M) and 3-isobutyl-1-methyl xanthine (10(-4) M) significantly and reversibly augmented the heat response. These results support the notion that cAMP is involved in the augmenting effect of PG E2 on the heat response of nociceptors.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Muscarinic receptor-mediated regulation of OM-853-enhanced dopamine release in striatum of rat.

The effect of OM-853, a new vincamine analogue, on cerebral dopaminergic neurons was investigated in male Wistar rats. The administration of OM-853 (200 mg/kg p.o.) induced facilitation of the metabolic turnover of dopamine (DA) in all brain areas except the cerebral cortex. Addition of OM-853 enhanced the release of [3H]DA from striatal slices; this release was antagonized by atropine (10(-7) M). However, pretreatment with scopolamine (0.5 mg/kg s.c.) inhibited the enhancement of striatal DA turnover induced by OM-853 administration. OM-853 (10(-4) M) inhibited [3H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in a striatal particulate fraction more potently than carbachol (10(-4) M). These results suggest that OM-853 may induce facilitation of striatal DA turnover by enhancing DA release via the stimulation of muscarinic cholinergic receptor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Electrical techniques for stimulation of the phrenic nerve to pace the diaphragm: inductive coupling and battery powered total implant in asynchronous and demand modes.

A review of the electrical design of a rf inductively coupled phrenic nerve stimulator for the diaphragm developed in our laboratories will be discussed. Modifications of the original circuit are based on long-term laboratory and clinical studies. A total implant battery powered stimulator was designed exclusively for animal studies to evaluate the effects of several stimulating parameters on diaphragm fatigue and neuromuscular structure. On the basis of these studies the optimum current level, stimulus frequency, respiratory rate, electrode configuration, and waveform were selected for clinical use to pace the diaphragm. A multiprogrammable dual output stimulator responsive to interrogation has been constructed and used in the experimental laboratory in anticipation of clinical application. There was an insignificant difference between the effect on neural structure or diaphragm function of stimulation with pulse width modulated constant voltage or with amplitude-modulated constant current. Demand pacing: maintenance of normal PACO2 by monitoring ET PACO2 with feedback to the diaphragm pacemaker to adjust the pacing rate has been successful in the experimental animal.

Animals↗
PubMed1989

Effect of buflomedil (4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxy phenyl)-1-butanone hydrochloride) on the function of striatal dopaminergic neurons.

Effect of buflomedil (4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxy phenyl)-1-butanone hydrochloride) on the release and uptake of dopamine (DA) and the function of DA receptors in the striatum was investigated using male Wistar rats. In vitro addition of buflomedil (10(-5)-10(-8) M) had no effect on the uptake of [3H]-DA in striatal slices. On the other hand, buflomedil (10(-5)-10(-7) M) increased the spontaneous as well as high K+ (30 mM)-evoked releases of [3H]DA from striatal slices. Buflomedil inhibited the bindings of [3H]SCH23390, [3H]spiperone and [3H]apomorphine to striatal D1, D2 and D3 receptors only at a high concentration. On the other hand, buflomedil inhibited [3H]quinuclidinyl benzilate (QNB) binding to striatal muscarinic cholinergic receptors, which was similar to the action of carbachol. Pretreatment with scopolamine (0.5 mg/kg) in vivo inhibited the facilitation of striatal DA turnover induced by oral administration of buflomedil (300 mg/kg). In contrast, continuous oral administration of buflomedil (30 mg/kg x 7 days) to rats had no significant effect on the specific bindings of [3H]SCH23390, [3H]spiperone, [3H]apomorphine and [3H]QNB to synaptic membrane preparations obtained from the striatum. These results suggest that buflomedil may enhance striatal DA release by stimulating muscarinic cholinergic receptor and that DA receptors may not be involved in the enhancing effect of buflomedil on DA release.

Animals↗
PubMed1989

Effect of (+/-)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo-[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (OM-853), a new vincamine analogue, on the metabolism and function of cerebral serotonergic neurons.

Effect of (+/-)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (OM-853), a new vincamine analogue, on the metabolism and function of cerebral 5-hydroxytryptamine (5-HT) neurons was investigated using male Wistar rats. The single administration of OM-853 (200 mg/kg, p.o.) induced the facilitation of metabolic turnover of 5-HT in various brain areas except the cerebral cortex, pons-medulla and cerebellum. In vitro addition of OM-853 inhibited the uptake of [14C]5-HT in striatal slices only at a high concentration (10(-4) M). On the other hand, a low concentration of OM-853 (10(-8)-10(-6) M) induced the increase of the spontaneous and high K+ (30 mM)-evoked releases of [14C]5-HT from striatal slices. OM-853 had more potent inhibitory effect on the binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-hydroxy DPAT) to 5-HT1A receptors and/or 5-HT autoreceptors than that of [3H]-ketanserin to 5-HT2 receptors. The stimulatory effect of OM-853 (10(-7) M) on [14C]5-HT release was antagonized by 10(-7) M 8-hydroxy DPAT, which is known to act at presynaptic 5-HT autoreceptors as an agonist. These results suggest that OM-853 may induce facilitation of 5-HT turnover by enhancing 5-HT release, probably via the inhibition of presynaptic 5-HT autoreceptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

[Effect of buflomedil on cerebral acetylcholine, neuroactive amino acids contents and energy metabolism: analysis using spontaneously hypertensive rat (SHR)].

Effects of continuous oral administration of Buflomedil on acetylcholine (ACh) and neuroactive amino acids contents and energy metabolism in the brain were investigated using Wistar Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). In both WKY and SHR, continuous oral administration of Buflomedil (30 mg/kg x 7 days) had no effect on ACh content in all cerebral areas examined. On the other hand, continuous oral administration of Buflomedil to SHR induced a significant increase in the contents of glutamic acid and taurine in the striatum and hypothalamus, while it resulted in a significant decrease in the contents of glycine and taurine in the midbrain and hippocampus. Glucose and ATP contents in the striatum of SHR showed a significant increase following the continuous oral administration of Buflomedil. These results suggest that Buflomedil may be a drug capable of improving various neuropsychiatric symptoms associated with cerebrovascular insufficiency by modifying the content of neuroactive amino acids and accelerating energy metabolism in the brain.

Acetylcholine↗
PubMed1988

[Emetic and catalepsy-inducing actions of buflomedil].

The emetic and catalepsy-inducing actions of buflomedil were studied in dog and mice. Oral administration of buflomedil (10-30 mg/kg) dose-dependently induced vomiting in dogs. On the other hand, the buflomedil-induced vomiting was inhibited by the pretreatment with domperidone (1 mg/kg, p.o.). A high dose of buflomedil (120-360 mg/kg, p.o.) induced catalepsy in mice, while a low dose of this agent (30-120 mg/kg, p.o.) had no enhancing effect on haloperidol-induced catalepsy. It was also found that the buflomedil-induced catalepsy was inhibited by the pretreatments with L-DOPA (300 mg/kg, i.p.) and bromocriptine (5 mg/kg, i.p.), respectively. These results suggest that buflomedil may induce emetic action as a dopamine agonist at a low dose, whereas it acts as a dopamine antagonist and a catalepsy inducer at a high concentration.

Administration, Oral↗
PubMed1988

Effect of buflomedil [4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone hydrochloride] on neurotransmitters in the striatum and substantia nigra.

Effect of buflomedil [4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone hydrochloride] administration on central monoaminergic systems was investigated using male Wistar rats. Single administration of buflomedil (300 mg/kg, p.o.) induced a significant increase in the content of homovanillic acid without altering the content of dopamine (DA) and also caused a significant decrease in choline acetyltransferase (ChAT) activity in the corpus striatum. In addition, both L-glutamic acid decarboxylase activity (GAD) and gamma-aminobutyric acid (GABA) content showed a significant decrease in the substantia nigra following a single administration of buflomedil. These results indicate that buflomedil enhances DA turnover in the nigro-striatal DA pathway, possibly by activating nigro-striatal DA neurons, or by suppressing striatal cholinergic interneurons and/or striato-nigral GABAergic neurons.

Amino Acids↗
PubMed1987

Synthesis and antimicrobial activity of cephalosporins with a 1-pyridinium substituent carrying a 5-membered heterocycle at the C-3 position.

A series of potent antimicrobial agents have been prepared. These derivatives are cephalosporins carrying a pyridine ring substituted with a heterocycle in the C-3 position. Some of them showed excellent activity not only against Gram-negative organisms including Pseudomonas aeruginosa but also against Gram-positive ones. In view of their biological and physico-chemical properties, 7 beta-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[4-(2 or 5-oxazolyl)-1-pyridinium]methyl-3-cephem-4-carboxylate 8f (DQ-2522) and 8g (DQ-2556) were chosen as candidates for further evaluation.

Cephalosporins↗
PubMed1985

Construction of rat-mouse T-cell hybridomas that constitutively produce rat IL-2.

We have established rat-mouse T-cell hybridomas that constitutively produce rat Interleukin-2 (IL-2). T-cell hybridomas cannot be boosted to a higher level of IL-2 production by Con A stimulation. IL-2 prepared from T-cell hybridomas and from Con A activated rat spleen cells was partially purified using Ultrogel AcA 54 chromatography and ion exchange chromatography on Mono Q or chromatofocusing on Mono P. When analyzed on Mono P, IL-2 activity derived from IA2-B10 T-cell hybridoma eluted as a single peak with pH range 6.9-7.1, whereas IL-2 derived from Con A activated spleen cells resolved into four peaks within the following pH range: 7.1-7.2, 6.5-6.6, 6.1-6.2, and 5.6-5.7. Neuraminidase-treated IL-2 derived from Con A activated spleen cells resolved into single peaks appearing in the pH range 7.1-7.2. In contrast, neuraminidase treatment did not change the elution profile of IL-2 derived from the IA2-B10 hybridoma. IL-2 activity derived from the 3D6-B1 T-cell hybridoma also eluted as a single peak with the pH range 7.1-7.2. Neuraminidase treatment did not change the elution profile of IL-2. These data demonstrate that heterogeneity of IL-2 might be due to differences in the degree of glycosylation of IL-2 and differences in the sources of T-cells from which the IL-2 has derived.

Animals↗