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H Kaneto

Publications and source records attributed to H Kaneto.

At least 109 records · Page 6Linked to original sources
PubMed1992

Participation of GABAergic systems in the production of antinociception by various stresses in mice.

Based on the data that diazepam, a benzodiazepine (BZP) receptor agonist, antagonized psychological (PSY)-stress induced analgesia (SIA) without prominent action on footshock (FS)- and forced swimming (SW)-SIA and that BZP receptors are coupled with GABA receptors, we examined how the GABAergic system participates in the production of various SIAs. Muscimol, a GABAA receptor agonist, at doses of 0.25 to 1.0 mg/kg, affected each SIA differently, suppressed PSY-SIA at 0.25 mg/kg but tended to potentiate it at 1.0 mg/kg, potentiated SW-SIA dose-dependently and did not affect FS-SIA at the doses employed. Both bicuculline, a GABAA receptor antagonist, 0.5 to 2.0 mg/kg, and picrotoxin, a Cl- channel blocker, 0.25 to 1.0 mg/kg, dose-dependently suppressed PSY- and FS-SIA. Meanwhile, the effects of both drugs on SW-SIA were less than those on PSY- and FS-SIA, namely, bicuculline slightly inhibited it only at 2.0 mg/kg, and picrotoxin did not produce any appreciable effect even at the highest dose. Baclofen, a GABAB receptor agonist, at 5.0 and 10.0 mg/kg had no influence on each SIA. On the contrary, CGP 35348, a GABAB receptor antagonist at 20 to 100 mg/kg caused the dose-dependent blockade of FS-SIA, but affected neither PSY- nor SW-SIA. The production of PSY- and SW-SIA is attributable to the GABAA receptors/Cl- channel mediated mechanism alone, while that of FS-SIA involves both GABAA and GABAB receptor mediated systems. Thus, GABAergic systems play an important role in the production of each SIA; however, the participation of the receptor subtypes in the mechanism was different from each other.

Analgesia↗
PubMed1991

Role of spinal kappa opioid receptors in the blockade of the development of antinociceptive tolerance to morphine.

The site of action of the kappa opioid receptor agonist, U-50,488H in suppressing the development of tolerance to morphine antinociception was examined by local application, either intrathecal (i.t., spinal) or intracerebroventricular (i.c.v., supraspinal) in mice. Mice given morphine s.c., i.c.v. or i.t. daily developed tolerance regardless of the route. Co-administration of U-50,488H i.p. at a subanalgesic dose suppressed the development of tolerance to s.c. and i.t. administered morphine without affecting the antinociceptive effect of morphine. U-50,488H did not influence the development of tolerance to i.c.v. administered morphine. The antinociceptive effect of s.c. administered morphine was not affected by co-administration of U-50,488H given i.t. or i.c.v.; however, the development of tolerance to morphine was suppressed by i.t. but not i.c.v. administered U-50,488H. The suppressive effect of U-50,488H on the development of tolerance to morphine was abolished by pretreatment with nor-binaltorphimine (nor-BNI) given i.p. or i.t. Intracerebroventricularly administered nor-BNI failed to abolish the effect of U-50,488H. We suggest that U-50,488H suppresses the development of tolerance to morphine at the spinal level by interacting with kappa opioid receptors in this area.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Three-D muscular arrangement at the ureteropelvic junction and its changes in congenital hydronephrosis: a stereo-morphometric study.

Ureteral walls were obtained from twelve autopsies without urological diseases and from surgical material of twelve patients operated for congenital hydronephrosis. The specimens were submitted to computer-assisted analysis of 3-D muscular architecture at the ureteropelvic junction (UPJ). Serial histologic sections in parallel with the wall were prepared. A geometric model was introduced to simplify the muscular layer, replacing bundles with vectors of corresponding size and direction. The vector distribution visualized that normally, the ureteral muscles change their arrangement with age, from a circular pattern in neonates to an oblique mesh in adults. In addition, longitudinal muscles emerged at the age of two years in the subepithelial layer. In patients with congenital hydronephrosis, not only were such growth-related changes ambiguous or lacking, but there also were various abnormalities; segmental muscular hypoplasia, disarrangement of bundles or lack of longitudinal fibers. These were considered to closely correlate with the urinary obstruction in patients with this disease.

Adolescent↗
PubMed1991

The opioid activity and receptor selectivity of fluorinated Leu5 enkephalin analogues in vitro and in vivo.

The opioid activity and the selectivity for opioid receptor (subtypes) of newly synthesized fluorinated enkephalin (Enk) analogues, [2R, 4R], [2R, 4S], [2S, 4S] and [2S, 4R] trifluoro-Leu5-Enk (KKF-31, 32, 33 and 34) were investigated. The inhibitory effect of KKF-compounds on the electrically induced contractions of guinea-pig ileum (GPI) and mouse vas deferens (MVD) were dose-dependent but relatively lower than that of L-Leu5-Enk, except that KKF-34 was rather slightly more potent than L-Leu5-Enk in MVD preparations. In GPI preparations, the pA2 values of naloxone for these compounds were higher than those of naltrindole while the values of naltrindole for KKF-compound were higher than those of naloxone in MVD preparations. Intracerebroventricular KKF-31 and KKF-32 at doses of 20 and 10 nmol/mouse, respectively, produced analgesia comparable to 0.1 nmol Tyr-D-Arg-Phe-Lys-NH2 and 100 nmol Tyr-D-Thr-Gly-Phe-Leu-Thr; however, neither KKF-33 nor 34 produced analgesia up to the doses of 100 nmol/mouse. Both naloxone, 1 mg/kg, i.p., and naltrindole, 10 mg/kg, i.p., antagonized KKF-31- and KKF-32-induced analgesia. The results suggest that the introduction of trifluoromethyl group in Leu5 results in the alternation of the opioid activity and receptor selectivity. Although KKF-33 and KKF-34 possessed a more potent in vitro inhibitory effect than KKF-31 and KKF-32, mediated through mu- and delta-opioid receptors in both preparations, they did not show any appreciable analgesic effect. KKF-31 and KKF-32 produce naloxone- and naltrindole-reversible analgesia irrespective of in vitro mu- and delta-opioid activity.

Analgesics↗
PubMed1991

Participation of an alpha 2-mediated mechanism in the production of forced swimming-stress induced analgesia in mice.

In mice, both swimming-stress induced analgesia (SW-SIA) and clonidine (CLO) analgesia were dose dependently antagonized by yohimbine, an alpha 2-adrenoceptor antagonist, but not by naloxone, an opioid mu-antagonist. SW-SIA was potentiated by subanalgesic dose of CLO, and CLO analgesia was enhanced by SW-SIA. Animals tolerant to CLO analgesia were tolerant to SW-SIA, in contrast, CLO analgesia was potentiated in SW-SIA tolerant mice. Thus, SW-SIA and CLO analgesia partially share a common alpha 2-adrenergic-dependent mechanism, for their production.

Analgesia↗
PubMed1991

Further evidence for the participation of an alpha 2-adrenoceptor mediated mechanism in the production of forced swimming-stress induced analgesia in mice.

Subanalgesic dose, 0.01 to 0.25 mg/kg, of clonidine (CLO), an alpha 2-adrenoceptor agonist, potentiated forced swimming (SW) stress induced analgesia (SIA) and suppressed psychological (PSY)-SIA in a dose dependent manner but did not affect foot-shock (FS)-SIA. Daily exposure to each stress rapidly developed tolerance, and the development was suppressed by daily concomitant subanalgesic dose of CLO in SW-SIA but not in FS- and PSY-SIA. Meanwhile, SW-stress, applied after injection of CLO, 1 mg/kg, potentiated the analgesic effect of CLO and suppressed the development of tolerance to the effect. On the other hand, FS- and PSY-stress did not affect CLO analgesia and failed to block the tolerance development. These results provide further evidence that alpha 2-adrenergic mechanism is involved in the production of SW-SIA.

Analgesia↗
PubMed1991

Differential roles of the adrenal gland in the suppression of morphine antinociceptive tolerance development by alpha- and beta-adrenergic blockers.

Concomitant treatment with phentolamine, an alpha-blocker, or with propranolol, a beta-blocker, suppressed the development of morphine tolerance in sham-operated (Sham) mice. In adrenalectomized (ADX) mice, daily morphine developed tolerance as well as in the Sham group, and concurrent phentolamine suppressed the development of tolerance, whereas such suppression by propranolol was abolished. Supplemental treatment of ADX mice with dexamethasone did not restore the suppressive effect of propranolol. These results suggest that different mechanisms underlie the prevention of tolerance development by alpha- and beta-blockers, and that adrenal cortex does not seem to participate in the suppression by beta-blockers.

Adrenal Glands↗
PubMed1991

Footshock- and psychological-stress prevent the development of tolerance to spinal but not supraspinal morphine.

The site of action involved in the suppression by exposure to footshock (FS)- and psychological (PSY)-stress of the development of antinociceptive tolerance to morphine has been investigated. Daily treatment with 10 mg/kg, s.c.; 3 micrograms, i.t.; and 5 micrograms, i.c.v. of morphine, regardless of the administration route, resulted in the development of tolerance. Daily exposure to FS- or PSY-stress suppressed the development of tolerance to s.c. and i.t. administered morphine but not that to i.c.v. administered morphine. Pretreatment with 2 mg/kg, i.p. of nor-binaltorphimine (nor-BNI) abolished the suppressive effect of PSY-stress on the development of tolerance to morphine given s.c. The suppression by PSY-stress was also antagonized by 2 micrograms, i.t. of nor-BNI and not by 2 micrograms, i.c.v. of nor-BNI. Thus, the development of tolerance in the spinal cord due to interaction of morphine at mu-opioid receptors can be suppressed by exposure to these stresses, probably through the descending signals from the supraspinal area, and activation of kappa-opioid receptors in the spinal cord could also participate in the suppression by PSY-stress.

Animals↗
PubMed1991

[Prostatic cancer with cystic degeneration: a case report].

A 73-year-old man with prostatic cancer with cystic degeneration is reported. He visited our clinic for postoperative examination of left metastatic lung cancer and treatment of prostatic hypertrophy. When the prostatic biopsy was performed, bloody fluid was aspirated and prostate size on digital examination was reduced. The obtained specimen consisted of scar tissue. Urethrography showed an elongation of prostatic urethra in addition to the compression of urinary bladder from the rear. CT scan demonstrated a prostatic cyst approximately 8 cm in diameter with an irregular margin. Following the transurethral resection of the prostate, the prostatic cyst was opened and papillary tumor observed. Histological examination revealed a well differentiated medullary cancer which coincided with the pathological finding of left metastatic lung cancer. He died from dyspnea caused by pleuritis carcinomatosa 6 years later. Nine cases of prostatic cancer with cystic degeneration in the Japanese literature are reviewed.

Adenocarcinoma↗
PubMed1990

Action site of adrenergic blockers to suppress the development of tolerance to morphine analgesia.

The effect of locally applied adrenergic blockers in the restricted area of the central nervous system on morphine analgesia and the development of tolerance to the analgesic effect was examined in the mouse. Intrathecal (i.t.) injection of phentolamine decreased the analgesic effect of morphine administered either subcutaneous (s.c.), intracerebroventricular (i.c.v.) or i.t., while i.t. propranolol was less potent in suppressing morphine analgesia and, in particular, did not affect the analgesic effect of i.t. morphine. I.c.v. phentolamine enhanced i.t. injected morphine analgesia; on the other hand, i.c.v. propranolol tended to reduce the analgesic effect of s.c. morphine. Compared with the effect on the analgesia, i.t. administration of both phentolamine and propranolol did not affect the development of tolerance to morphine and i.p. or i.c.v. blockers suppressed the development of tolerance to s.c. or i.t. morphine analgesia. Moreover, morphine tolerance induced by i.c.v. administration was blocked by i.c.v. phentolamine. These results not only provide further evidence for the importance of the spinal and supraspinal adrenergic systems in the analgesic effects of morphine and the development of tolerance to the effect, respectively, and also suggest the difference in both the site and mechanisms involved in the production of morphine analgesia and the development of tolerance to morphine.

Adrenergic alpha-Antagonists↗
PubMed1990

Facilitation of memory retrieval by pretest morphine mediated by mu but not delta and kappa opioid receptors.

Mice were trained to avoid electric shock (0.6 mA) in a step-through type passive avoidance learning task, retention being measured 24 h after the training trial. Morphine 10 mg/kg administered 30 min before the test trial (pretest) facilitated memory retrieval, and the effect was completely antagonized by 1 mg/kg naloxone, a selective mu-opioid receptor antagonist. On the other hand, pretest administration of 0.01-10 mg/kg DTLET, a selective delta-opioid receptor agonist, did not produce the same effect as morphine. Nor-binaltorphimine, a kappa-opioid receptor antagonist, did not antagonize the effect of pretest morphine, at doses of 1 and 2 mg/kg. These results suggest that the facilitation of memory retrieval by pretest morphine is mediated through mu- but not delta- or kappa-opioid receptors.

Analgesics↗
PubMed1990

State dependent and/or direct memory retrieval by morphine in mice.

Mice were trained in step-down and step-through type passive avoidance learning tasks and given retention tests. Pre-training administration of morphine impaired retention, the effect recovering completely after an additional injection of the same dose of morphine given 30 min before the retention test. Amnesia produced by scopolamine, cycloheximide and electroconvulsive shock was also reversed by pre-test morphine. Pre-test saline also reversed the morphine-induced memory impairment to some extent, indicating that the recovery may partially be due to the state dependent effect. Thus, it is demonstrated that pre-test morphine not only state dependently but also directly reversed memory impairment in mice.

Amnesia↗
PubMed1990

The opioid receptor selectivity for trimebutine in isolated tissues experiments and receptor binding studies.

Differences of affinity to and selectivity for trimebutine between peripheral and central opioid receptors have been investigated. Trimebutine inhibited electrically induced contraction of guinea-pig ileum (GPI) and mouse vas deferens (MVD) but not of rabbit vas deferens, and the inhibition was antagonized by naloxone and, to lesser extent, by nor-binaltorphimine (nor-BNI). The pA2 values for morphine and trimebutine with naloxone were higher than the values for these compounds with nor-BNI in both GPI and MVD preparations. GPI preparations incubated with a high concentration of morphine or trimebutine developed tolerance; however, there was no cross-tolerance between them, suggesting difference in the underlying mechanisms. In mouse and guinea-pig brain homogenate trimebutine was about 1/13 as potent as morphine to displace the [3H]naloxone binding, while it has no appreciable affinity for kappa-opioid receptors in [3H]U-69593, a selective kappa-receptor agonist. These results suggest that trimebutine, showing its low affinity to opioid receptors, possesses mu-receptor selective properties rather than those of kappa-opioid receptor in the peripheral tissues and in the central brain homogenate.

Animals↗
PubMed1990

Effect of straight chain fatty acids on seizures induced by picrotoxin and pentylenetetrazole in mice.

The effects of straight chain fatty acids on seizures induced by picrotoxin and pentylenetetrazole were studied in mice. After i.p. injection capric, lauric, myristic, palmitic and stearic acid delayed the onset of picrotoxin-induced clonic convulsion in a dose-dependent manner. The survival time was also prolonged by the pretreatment with lauric, myristic, palmitic and stearic acid. However, the onset of the clonic convulsion induced by pentylenetetrazole was delayed only by lauric acid. The prolongation of the survival time was also observed only in the animals pretreated with capric and lauric acid. These results suggest that the straight chain fatty acids examined in the present study possess anticonvulsant activity in mice.

Animals↗
PubMed1990

Dual action mechanisms of KK-3, a newly synthesized leu-enkephalin derivative, in the production of spinal analgesic effects.

The action mechanism for the production of spinal analgesia of KK-3, tyrosyl-N-methyl-gamma-aminobutylyl-phenylalaninol, was examined by the tail pinch and tail flick methods. Intrathecal KK-3, 2.5, 5 and 10 nmol/mouse, dose-dependently produced an analgesic effect in both methods. In the tail pinch method, the analgesia was suppressed by 2 mg/kg but not by 1 mg/kg of naloxone; however, the analgesic effect was significantly antagonized by 1 and 2 mg/kg Mr2266, a kappa-antagonist. Meanwhile, both naloxone and Mr2266 failed to block the analgesic effect of KK-3 in the tail flick test. Intrathecal capsaicin, 0.3, 3 and 15 nmol/mouse, also produced a dose-dependent analgesic effect in the tail flick test, whereas no appreciable analgesia could be found in the tail pinch test. Neither naloxone nor Mr2266 blocked the analgesic effect of capsaicin. The results indicate that KK-3 may possess two separate pharmacological mechanisms for the production of analgesic effects on the spinal level: one is the depletion of substance P following its release from the spinal cord, and the other is the mediation through kappa-opioid receptors.

Analgesics↗
PubMed1990

Further evidence for the implication of a kappa-opioid receptor mechanism in the production of psychological stress-induced analgesia.

The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, PSY-SIA), was completely antagonized by 10 min pretreatment with 0.5, 1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective kappa-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)- nor forced swimming (SW)-SIA was affected by these antagonists. The selective delta-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on PSY-SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to PSY-stress suppressed the development of morphine tolerance. The substitution of treatment with U-50,488H for PSY-stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50,488H of the development of morphine tolerance was replicated by PSY-stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of PSY-stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that PSY-SIA involves the mediation by kappa-opioid receptor mechanisms.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice.

Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.

Amnesia↗