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Biomedical subjects

T Katsuragi

Publications and source records attributed to T Katsuragi.

At least 91 records · Page 5Linked to original sources
PubMed1987

Different mechanisms of the rabbit pulmonary arterial contraction caused by 5- or 6-hydroxydopamine.

The contractile responses of rabbit arterial strips to 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were assessed in vitro. The 3H efflux from the pulmonary artery after preloading with [3H]noradrenaline was markedly enhanced by 100 microM 5-OHDA or 6-OHDA. In non-superfused strips, 6-OHDA produced a biphasic contraction, an initial small transient and a subsequent large sustained contraction, whereas 5-OHDA elicited a large monophasic contraction. The 6-OHDA-evoked second large contraction was followed by a marked tachyphylaxis after repeated application of the drug. This contraction was greatly diminished by prazosin or cocaine and by pretreatment with reserpine, indicating an indirect action via noradrenaline release. In contrast, the initial contraction caused by 6-OHDA as well as the contraction caused by 5-OHDA was not inhibited by these agents, except prazosin, implying a direct action at the postsynaptic alpha 1-adrenoceptors. In addition, the concentration-response curve for noradrenaline was significantly shifted to the right by pre-addition of 5-OHDA whereas the curve for 5-HT was virtually unaffected. The results thus suggest that 5-OHDA acts as a postsynaptic alpha 1-adrenoceptor agonist.

Animals↗
PubMed1987

Release of purines and noradrenaline from the vascular adrenergic nerves by 5- and 6-hydroxydopamine.

1. The in vitro effects of 6-hydroxydopamine (6-OHDA) and 5-hydroxydopamine (5-OHDA) on 3H-efflux from rabbit pulmonary artery after incubation with [3H]noradrenaline ([3H]NA) or [3H]adenosine were assessed. 2. 6-OHDA (100 microM) or 5-OHDA (100 microM) enhanced not only [3H]noradrenaline efflux, but also [3H]purines efflux. 3. Following Ca2+-removal, [3H]NA and [3H]purine effluxes evoked by these hydroxydopamines were moderately and considerably diminished, respectively. In addition, the 6-OHDA-evoked [3H]purine efflux was significantly decreased by W-7 (30 microM), a calmodulin inhibitor. 4. The 6-OHDA or 5-OHDA-evoked purine release was almost insensitive for prazosin (0.3 microM), indicating a neuronal release. 5. The peak [3H]purine efflux evoked by 6-OHDA or 5-OHDA occurred in the corresponding fraction number to that for the [3H]NA efflux. 6. These results suggest that 6-OHDA and 5-OHDA may expel NA together with purines from the amine stored sites (probably, in axoplasm) in the adrenergic nerves.

Adenosine↗
PubMed1986

Clonidine-evoked selective P1-purinoceptor antagonism of contraction of guinea-pig urinary bladder.

The effect of clonidine on P1- and P2-purinoceptors of guinea-pig urinary bladder was compared to that of alpha, beta-methylene ATP, a selective P2-purinoceptor desensitizer. After, alpha, beta-methylene ATP, 10 microM, vesical contraction produced by ATP was eliminated while that caused by acetylcholine was unaffected. Clonidine, however, failed to antagonize ATP-induced contraction of the segment even at 100 microM. Electrically evoked contraction of the bladder was partly attenuated by 0.3 microM atropine and the remainder was markedly reduced by 3-30 microM alpha, beta-methylene ATP, suggesting an important role of ATP as an excitatory transmitter in this tissue. This stimulus-evoked contraction was also suppressed by adenosine, a P1-purinoceptor agonist, in a concentration-dependent fashion, and the suppression was greatly antagonized by 50 microM clonidine. These results suggest that the antagonistic property of clonidine is substantially selective for presynaptic P1-purinoceptors in contrast with that of alpha, beta-methylene ATP for postsynaptic P2-purinoceptors.

Adenosine Triphosphate↗
PubMed1986

Contribution of Na+ and membrane depolarization to contraction induced by adrenaline in the guinea pig vas deferens.

The contribution of Na+ and membrane depolarization to biphasic contractions induced by adrenaline were investigated in the smooth muscle of guinea pig vas deferens. Adrenaline (5 X 10(-6) M) produced an initial small contraction (first contraction) followed by a large tonic contraction (second contraction) with subsequent rhythmic activity. The entire response to adrenaline was largely inhibited by phentolamine (5 X 10(-6) M). By adding an appropriate concentration of Mn2+ (2 X 10(-4) M) or nifedipine (3 X 10(-7) M), a Ca2+ blocker, the second contraction was strongly reduced, accompanied by abolishment of the rhythmic contraction, whereas the first contraction was virtually unaffected. However, the first contraction was markedly suppressed by a higher concentration of Mn2+. All contractions produced by adrenaline were greatly reduced in Ca2+-free solution containing 0.5 mM EGTA. By lowering external Na+ concentration, the first contraction was markedly increased without greatly affecting the second contraction. By exposure to Na+-free isotonic high K+ solution, which elicited a greater depolarization of the membrane, the first contraction produced by adrenaline was also greatly potentiated, while the second and rhythmic contractions were eliminated. These results suggest that the adrenaline-evoked first contraction may be due to an influx of membrane bound Ca2+ which is independent of membrane depolarization, while the second (rhythmic) contraction is due to an influx of extracellular Ca2+ which is dependent upon depolarization.

Animals↗
PubMed1986

Release of acetylcholine mediated by cholecystokinin receptor from the guinea pig sphincter of Oddi.

Mechanisms involved in the action of cholecystokinin octapeptide (CCK-8) on the isolated circular muscle of the guinea pig sphincter of Oddi were investigated. CCK-8 (10(-9) to 10(-6) M) caused a concentration-dependent contraction of the sphincter. Angiotensin II, bethanechol and serotonin also contracted this tissue. CCK-8 exerted the most potent effect. However, bradykinin, porcine motilin and norepinephrine failed to elicit any contraction. The CCK-8-induced contraction was inhibited by about 60% by atropine (3 X 10(-7) M) or tetrodotoxin (3 X 10(-7) M) but was not affected by hexamethonium (3 X 10(-5) to 10(-4) M) or phentolamine (3 X 10(-6) to 10(-5) M). Proglumide (3 X 10(-4) to 3 X 10(-3) M), a derivative of glutaramic acid, inhibited competitively the contraction by CCK-8. However, proglumide influenced neither the electrically elicited twitch contraction nor the bethanechol-induced contraction. CCK-8 evoked a concentration-related release of [3H]acetylcholine (ACh) from previously labeled stores. The CCK-8-evoked release of [3H]ACh was eliminated by tetrodotoxin and was inhibited, in a concentration-dependent manner, by proglumide. These results suggest that the contractile response to CCK-8 of the guinea pig sphincter of Oddi consists of a direct effect on the smooth muscle and an indirect effect mediated by ACh release from postganglionic parasympathetic neurons.

Acetylcholine↗
PubMed1985

Antagonism by clonidine of the adenosine-induced inhibition of the twitch contraction of the guinea-pig Oddi sphincter.

The effects of clonidine on the purinergic inhibition of cholinergic transmission were investigated; we used the twitch contraction of a circular segment of the guinea-pig Oddi sphincter stimulated electrically. A circular segment of Oddi sphincter was contracted in a frequency-dependent manner by transmural nerve stimulation. Adenosine (10(-6) to 10(-4] produced a reduction of approximately 40% in the twitch contraction elicited at 5 Hz. The inhibition was antagonized by theophylline (10(-5) M), 8-phenyltheophylline (10(-6) M) or clonidine (10(-6) to 3 X 10(-6) M) but was enhanced by dipyridamole (3 X 10(-6) M). This antagonism produced by clonidine (3 X 10(-6) M) was almost unaffected by yohimbine (3 X 10(-6) M). The twitch contraction was also suppressed by N6-substituted adenosine analogs, L-PIA and CHA. The suppression was counteracted by theophylline or clonidine. The contraction produced by exogenously administered acetylcholine was not affected by clonidine and/or adenosine at all. The results suggest that clonidine, like theophylline, seems to exert these antagonistic effects by acting on the neuronal adenosine receptors in the guinea-pig Oddi sphincter muscle.

Adenosine↗
PubMed1985

A possible explanation for a greater discrepant suppression by adenosine and N6-cyclohexyl adenosine of the guinea-pig ileal contraction.

Adenosine and N6-cyclohexyl adenosine (CHA) reduced dose-dependently a twitch contraction of guinea-pig ileum and their IC50 values were 1.0 X 10(-5) and 1.1 X 10(-8) M, respectively. By exposure to adenosine uptake and deaminase inhibitors, dipyridamole and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), the adenosine-induced inhibition was enhanced, whereas the CHA-induced one was almost unchanged. Therefore, outstanding potency difference of the suppression by adenosine and CHA was minimized by concurrent addition of both the inhibitors. Uptakes of [3H]CHA into the guinea-pig ileum and taenia-coli were considerably lower than those of [3H]adenosine and were insensitive to dipyridamole. In the rat connective tissue segment, uptake of [3H]adenosine was smaller than that in the guinea-pig taenia-coli and ileal segments (especially, in the latter), and was virtually unaffected by 10(-5) M dipyridamole. These findings suggest that a greater discrepancy of the suppression by adenosine and CHA of the ileal twitch may substantially result from their different uptake and deamination in the synaptic region rather than their dissimilar intrinsic activity for the purinoceptor.

Adenosine↗
PubMed1985

Antineoplastic effects in rats of 5-fluorocytosine in combination with cytosine deaminase capsules.

5-Fluorocytosine (5-FC) lacks antineoplastic activity in human subjects because of the absence of cytosine deaminase (CDase) in mammalian cells. Intratumoral conversion of 5-FC into 5-fluorouracil (5-FUra) by locally implanted capsules containing CDase followed by systemic administration of 5-FC can be expected to induce antineoplastic activity at a local site with minimal systemic toxicity. In vitro and in vivo experiments were performed to evaluate this hypothesis. Spectrophotometric analysis confirmed the deamination of 5-FC to 5-FUra by CDase extracted from cultivated Escherichia coli. In vitro studies showed that 5-FC combined with CDase induced significant growth-inhibitory effects on the cultured glioma cells. An active CDase capsule, made of cellulose tubing, was newly designed for local implantation. 5-FC concentrations in the s.c. tumors of the rats given these CDase capsules, followed by 5-FC administration, showed a sufficient amount of delivery of 5-FC to the tumor tissue. 5-FUra appearing in the tumor reached the level of 8.0 micrograms/g at 2 h and stayed at more than 1.0 microgram/g at between 1 and 6 h. Significant reduction of the tumor growth and cytotoxic changes were observed. The passive cutaneous anaphylaxis reaction demonstrated no allergic reaction to the host due to the capsule. These results suggest that this chemotherapeutic method is effective for human brain tumors.

Animals↗
PubMed1984

Involvement of adenosine receptor activities in aggressive responses produced by clonidine in mice.

A behavioral study was made of the mechanisms underlying the aggressive behavior induced by high doses of clonidine in mice. The frequency of clonidine-induced aggressive responses such as attacking and biting was increased dose-dependently from 10 to 50 mg/kg. Aggressive behavior induced by clonidine at doses of 10-30 mg/kg was potentiated under conditions of isolation and food deprivation for 24 h. Clonidine (30 mg/kg)-induced aggressive behavior was attenuated by adenosine (10 mg/kg IP) or dipyridamole (10 mg/kg IP), but markedly antagonized by combined pretreatment with both drugs. The behavior was strongly reduced by potent adenosine analogs, such as N6-cyclohexyl adenosine (CHA, 0.1 and 0.2 mg/kg IP) and N6-(L-phenyl isopropyl) adenosine (L-PIA, 0.2 mg/kg IP), but conversely was potentiated by phentolamine (10 mg/kg IP) or theophylline (10 mg/kg IP). Diazepam (2.5 mg/kg IP) and Ro15-1788 (2.5 mg/kg IP), a benzodiazepine receptor antagonist, also blocked the aggressive behavior. The inhibition by CHA (0.2 mg/kg IP) or diazepam (2.5 mg/kg) of clonidine-induced aggression was not antagonized by additional pretreatment with bicuculline (2 mg/kg IP). The aggressive response to apomorphine (8 mg/kg IP) was not affected by those drugs which inhibited the response to clonidine. The results suggest that the aggressive behavior evoked by high doses of clonidine, but not that by apomorphine, involves a blockade of adenosine receptors.

Adenosine↗
PubMed1984

The clonidine-induced self-injurious behavior of mice involves purinergic mechanisms.

Mode of action of clonidine involved in self-injurious behavior was assessed in mice. Single injection of clonidine (50 mg/kg, IP) evoked a self-biting which occurred more frequently under the condition of isolation and food-deprivation for 24 hr. The clonidine-induced self-biting was not reduced, but rather potentiated by pretreatment with phentolamine (10 mg/kg). This behavior was enhanced by theophylline (20 mg/kg) but was inhibited to some extent by adenosine (10 mg/kg) or dipyridamole (10 mg/kg). In addition, the self-injurious behavior was completely antagonized by combined pretreatment with adenosine (10 mg/kg) and dipyridamole (10 mg/kg), and by potent adenosine agonists, such as N6-(L-phenylisopropyl) adenosine (0.2 mg/kg) and N6-cyclohexyladenosine (0.2 mg/kg). These results, therefore, suggest that the clonidine-induced self-biting could be substantially attributed to adenosine A1-receptor blockade as documented for pharmacological property of theophylline in the brain.

Aggression↗
PubMed1984

Calcium antagonistic action involved in vasodilation by brovincamine.

Possible mode of vasodilative action of brovincamine was assessed in isolated cardiovascular preparations in comparison with verapamil and papaverine. Brovincamine (IC50: 1.2 x 10(-5) M), verapamil (IC50: 3.5 x 10(-7) M) or papaverine (IC50: 2.5 x 10(-5) M) caused a dose-dependent relaxation of potassium (30 mM)-contracture in the rabbit pulmonary arterial segment. This relaxation by verapamil or brovincamine, but not by papaverine, was antagonized by increasing external Ca2+ concentration to 12.4mM. Duration of slow action potentials of partially depolarized guinea-pig papillary muscle was reduced by 14 min exposure to brovincamine (5 x 10(-5) M) or verapamil (10(-5) M. These results suggest that brovincamine produces a vasodilation via a slow Ca2+-channel blockade.

Action Potentials↗
PubMed1984

Effects of brovincamine on the autonomic nervous function in the dog and rat.

Effects of brovincamine (BV) on peripheral nerves were studied in dogs and rats. 1) In pentobarbital-anesthetized dogs, BV (6.4 mg/kg) administered i.v. did not affect the changes of blood pressure and heart rate induced by noradrenaline and adrenaline, but slightly inhibited the hypotensive effect of acetylcholine. BV had no effect on the hypertension elicited by carotid sinus reflex, but diminished the bradycardia by vagus nerve stimulation. BV did not influence the tachycardia elicited by stimulation of the postganglionic nerve to stellate ganglion, but slightly inhibited that by the preganglionic stimulation. 2) In spinal dogs, BV (6.4 mg/kg) given i.v. slightly inhibited the increases of blood pressure and heart rate induced by i.v. dimethylphenylpiperazinium (DMPP). When i.v. administered in divided doses of 2 and 4 mg/kg, BV induced a slight but stepwise inhibition of the tachycardia elicited by direct administration of DMPP, bethanechol (BCH) and angiotension II (AT II) to the cardiac sympathetic ganglia via the subclavian artery. 3) In rat isolated diaphragm nerve preparations, BV at 10(-5) and 10(-4) g/ml dose-dependently reduced the twitch response to nerve stimulation. 4) In conclusion, BV does not affect the sympathetic activities but inhibits the cholinergic function in the autonomic nervous system.

Acetylcholine↗
PubMed1983

Discrimination by dipyridamole of two types of responses to adenosine and ATP of the carbachol-induced contraction of guinea-pig trachea.

Two types of effect of purines on the carbachol-induced contraction of the guinea-pig trachea in the presence or absence of glucose were evaluated using dipyridamole, and adenosine uptake inhibitor. ATP exerted a greater relaxant effect on the carbachol (10(-6) M)-induced contraction than did adenosine in concentrations ranging from 10(-4) to 10(-3) M. These effects of purines were enhanced by pretreatment with dipyridamole (10(-5) M) but were virtually unaffected by the purine receptor antagonists theophylline (10(-5) M) and quinidine (10(-5) M). The contraction evoked by carbachol was gradually reduced and was almost abolished 4-5 h after exposure to the glucose-free solution. This reduction was almost eliminated by readmitting glucose, and was restored to a certain degree by introducing ATP or adenosine. ATP was less effective than adenosine. This effect of purines but not that of glucose, was markedly diminished by pretreatment with dipyridamole (3 X 10(-6) M to 10(-5) M). The restoration of the carbachol-induced contraction following introduction of purines or glucose was completely antagonized by atropine (10(-6) M). These results suggest that the extracellular effects of adenosine and ATP on the carbachol-induced contraction in normal solution are potentiated by dipyridamole, whereas the possible intracellular effects of these purines in the glucose-free solution are inhibited by this adenosine uptake inhibitor.

Adenosine↗
PubMed1982

Mechanism of extraneuronal adrenaline release induced by K+-free medium and ouabain, but not by high KCl in vas deferens of guinea-pig and rat.

The effects of K+-free medium, ouabain or high KCl on the contractile response and spontaneous efflux of adrenaline were analyzed in denervated guinea-pig or rat vasa deferentia preloaded with 3 x 10(-5) M (+/-)-adrenaline. The K+-free medium-induced contraction of guinea-pig tissues was related to the concentration of adrenaline used during preloading and was suppressed by the addition of 2.5 mM Rb+ but not by 2.5 mM Cs+. The contractile effects of K+-free medium and 10(-5) M ouabain, but not the response to high KCl, were prevented by 5 x 10(-6) M phentolamine or 3 x 10(-5) M deoxycorticosterone. These contractions, therefore, appear to be mediated by adrenaline released from the extraneuronal compartment. The K+-free medium- or ouabain-induced contractions of denervated rat vasa deferentia were small in comparison with those of the guinea-pig tissue. The amount of spontaneous efflux of adrenaline from the guinea-pig preparation was significantly enhanced by omission of K+ or by 10(-4) M ouabain but not by 80 mM KCl. K+-free medium and 3 x 10(-5) M ouabain merely elicited a small membrane depolarization accompanied by a slight decrease of membrane resistance in the guinea-pig vas deferens, whereas 30 mM KCl markedly altered these electrical parameters. From these findings, it is suggested that the rapid increase in extraneuronal amine release following inhibition of Na+-K+-ATPase may be due to some direct effect of K+ deficiency or of ouabain on the binding between the enzyme and the catecholamine rather than to alterations of membrane properties as a consequence of enzyme inhibition.

Animals↗
PubMed1982

Possible selective inhibition of [3H]adenosine uptake by papaverine in vascular adrenergic nerves.

The effect of the adenosine uptake inhibitors dipyridamole, papaverine and diazepam on the [3H]adenosine uptake was assessed using the rabbit pulmonary arterial segment. [3H]Adenosine uptake into the vascular segment was significantly diminished by dipyridamole (10(-6) -10(-5) M), papaverine (10(-5) -10(-4) M) or diazepam (5 x 10(-5) M) with potencies: dipyridamole greater than papaverine greater than diazepam. Dipyridamole (10(-6) M) or diazepam (5 x 10(-5) M) added 30 min before the incubation with [3H]adenosine reduced the high KCl-induced and epinephrine-induced [3H]purine effluxes equally, whereas papaverine (10(-5) M) selectively diminished the former efflux. KCl and epinephrine have been shown to act preferentially on the neuronal and extraneuronal sites, respectively. These results suggest that papaverine inhibits adenosine uptake into the vascular neuronal compartment, in preference to that into the extraneuronal compartment.

Adenosine↗
PubMed1982

Release of purines and noradrenaline by ouabain and potassium chloride from vascular adrenergic nerves.

1 Release of [3H]-noradrenaline and 3H-purine by ouabain (10(-4)M) or high KCl (50 mM) was investigated in the superfused rabbit pulmonary arterial segment preincubated with [3H]-noradrenaline or [3H]-adenosine. 2 Ouabain elicited a delayed large contraction and a parallel [3H]-noradrenaline efflux. These were substantially inhibited by Ca2+-free medium or preincubation with 6-hydroxydopamine (30 micrograms/ml, 30 min). 3 Ouabain caused an 3H-purine efflux which was slower than the [3H]-noradrenaline efflux. This was inhibited by 6-hydroxydopamine and in part by phentolamine (3 X 10(-6)M), indicating both neuronal and extraneuronal origins of purines. 4 In contrast to ouabain, high KCl appeared to induce predominantly purine efflux, which was phentolamine-insensitive and 6-hydroxydopamine-sensitive, indicative of neuronal origin. 5 It is suggested that the purine efflux evoked by ouabain and high KCl may originate from different neuronal vesicles.

Animals↗
PubMed1982

Augmentation by theophylline of [3H]purine release from vascular adrenergic nerves: evidence for presynaptic autoinhibition.

The effect of theophylline (a P1-purinoceptor blocker) on the tritium release evoked by high KCl (50 mM) and l-epinephrine (3 microM) was evaluated using [3H]adenosine-prelabeled pulmonary artery of the rabbit. It has previously been shown that KCl elicits purine release from adrenergic nerve terminals whereas epinephrine releases it from postsynaptic sites in this artery. The KCl-induced [3H]purine efflux was significantly enhanced by theophylline (10-100 microM), whereas the efflux induced by epinephrine (3 microM) was not enhanced but reduced by this drug at 100 microM. In contrast to theophylline, 1 to 3 microM adenosine or ATP significantly suppressed the KCl-induced purine efflux. This depolarization-induced efflux was not augmented by 10 microM papaverine or 3 microM phentolamine. Uptake of [3H]adenosine into the pulmonary arterial segment was strongly inhibited by 10 microM dipyridamole or papaverine, but not by the same concentration of theophylline. These findings suggest that the presynaptic autoinhibition mechanism may be involved in the purine release from vascular adrenergic nerves.

Adenosine↗