Search PubMed⌕ Search

Biomedical subjects

K Kisara

Publications and source records attributed to K Kisara.

At least 127 records · Page 7Linked to original sources
PubMed1986

The ex vivo effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on rat intra- and extraneuronal monoamine oxidase activity.

After i.p. injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) daily for 4 days and sacrificing the rats 4 h after the last injection, striatal monoamine oxidase (MAO)-A and -B activities, assayed by conventional method with 5-hydroxytryptamine (5-HT) and benzylamine, were not changed. By an uptake technique, with dopamine as the substrate for both uptake and MAO, intrasynaptosomal MAO-A and -B activities were found to be greatly reduced with a greater MAO-A reduction. Intrasynaptosomal 5-HT oxidation by MAO-A was not changed in other forebrain regions treated with these MPTP doses. Similar results were also found with two brain preparations treated with single MPTP doses (30 mg/kg). This reduction in intrasynaptosomal MAO activity was completely absent after treatment with lower MPTP doses (15 mg/kg, daily for 5 days) and 5 days of a withdrawal period. The decrease in MAO activity might have been due to the decrease in DA transport into striatal synaptosomes during the enzyme assay and/or to reversible inhibition of intrasynaptosomal MAO by MPP+.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Inhibition of rat brain monoamine oxidase by some analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion.

To clarify the essential chemical structures of the neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its oxidized product, 1-methyl-4-phenylpyridinium ion (MPP+), that govern nigrostriatal dopamine neuron toxicity, interactions of several structurally related compounds of MPTP or MPP+ with monoamine oxidase (MAO) in rat forebrain homogenates were studied. Of the compounds tested, 4-phenyl-1,2,3,6-tetrahydropyridine (PTP), 4-phenylpyridine and 4-phenylpiperidine strongly and dose-dependently inhibited MAO-A and -B activity. Inhibition of PTP and 4-phenylpiperidine was MAO-A-selective, while that by 4-phenylpyridine was MAO-B-selective. Of these 3 compounds, only PTP time-dependently inhibited MAO-B, but not -A. Without preincubation, the modes of inhibition of MAO-A and -B by PTP were competitive. After 1 h preincubation, the mode of MAO-B inhibition changed to non-competitive, while inhibition of -A remained unchanged. PTP was oxidized by MAO-B, but not by -A, under these conditions. In contrast, 4-phenylpyridine and 4-phenylpiperidine were not substrates for either form of MAO in rat forebrain homogenates. These results, along with the other observations, indicate that PTP may essentially cause a neurotoxic effect on the nigrostriatal dopamine pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Physical dependence of a dermorphin tetrapeptide analog, [D-Arg2, Sar4]-dermorphin (1-4) in the rat.

The characteristics of an analog of tetrapeptide dermorphin (H-Tyr-D-Arg-Phe-Sar-OH), [D-Arg2, Sar4]-dermorphin (1-4) were examined in comparison with morphine by the appearance of typical withdrawal signs upon cessation of administration or treatment with naloxone, an opioid antagonist. The dose of [D-Arg2, Sar4]-dermorphin (1-4) or morphine in the physical dependence test can be quantified by determining the ED50 to inhibit the tail-flick response to thermal stimuli. Doses from 8 to 64 times the ED50 doses were employed in the subcutaneous injection schedules. The cessation of [D-Arg2, Sar4]-dermorphin (1-4) or naloxone treatment was largely without effect on body weight, in contrast to a marked loss of weight in morphine-dependent rats. The tetrapeptide failed to substitute for morphine in morphine-dependent rats. The physical dependence of [D-Arg2, Sar4]-dermorphin (1-4) was revealed by the behavioral signs of withdrawal precipitated by naloxone. However, the scores of lacrimation, diarrhea and urination were much lower in chronically tetrapeptide-treated rats than in morphine-treated rats, though the score of teeth chatter was higher. These findings indicate that [D-Arg2, Sar4]-dermorphin (1-4) may differ from morphine in physical dependence.

Analgesics↗
PubMed1986

Dermorphin analogues containing D-kyotorphin: structure-antinociceptive relationships in mice.

The antinociceptive effects of synthetic dermorphin and its analogues containing D-Arg in position 2 injected into the lateral cerebroventricle were examined in conscious mice. Intracerebroventricular (i.c.v.) administration of dermorphin and [D-Arg2] dermorphin produced potent and long-lasting antinociceptive activity as assayed by the tail-pressure test. Dermorphin and [D-Arg2] dermorphin were 210 and 52 times more potent than morphine, respectively. The antinociceptive effects produced by these heptapeptides were antagonized by a low dose (0.5 mg kg-1, i.p.) of the opioid antagonist naloxone. The ED50 values for [D-Arg2] dermorphin (1-6), (1-5) and (1-4) were not significantly different from that for [D-Arg2] dermorphin. The potency of the shortest fragment, [D-Arg2] dermorphin (1-2) was found to possess a severely reduced activity, whilst [D-Arg2] dermorphin (1-3) maintained activity and was 10 times more potent than morphine. [D-Arg2] dermorphin analogues showed almost identical effects when tested on the electrically-induced contractions of the guinea-pig isolated ileum. These results led us to conclude that the presence of the N-terminal tripeptide in the structure of [D-Arg2] dermorphin is of crucial importance for the manifestation of the full intrinsic opioid-like antinociceptive activity of [D-Arg2] dermorphin, which is presumably mediated through opioid receptors in the brain.

Analgesics, Opioid↗
PubMed1986

Potentiation of dermorphin-induced antinociception by peptidase inhibitors.

We have investigated the effect of amastatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, on the antinociceptive activity induced by intracerebroventricular administration of dermorphin, a heptapeptide. In addition, the potency of dermorphin was compared with that of one of its metabolites, N-terminal tetrapeptide (Tyr-D-Ala-Phe-Gly), by using the tail pressure test. The antinociceptive activity induced by dermorphin was not potentiated by simultaneous administration of amastatin or captopril. However, there was potentiation when dermorphin was combined with both peptidase inhibitors. Moreover, the N-terminal tetrapeptide was 84 times less potent than its parent heptapeptide when administered intracerebroventricularly. The results suggest that the cleavage of Tyr1-D-Ala2 and Gly4-Tyr5 bonds by brain endopeptidase modulates dermorphin-induced antinociceptive activity.

Analgesics↗
PubMed1986

Evidence for central alpha2-adrenergic mechanism of clonidine-induced ejaculatory disturbance in dogs.

In order to clarify the central mechanism of clonidine (CL)-induced sexual dysfunction such as erectile and ejaculatory disturbances, we examined the effects of intracerebroventricularly (i.c.v.) administered CL on erection and ejaculation in male dogs. CL (0.5-5 micrograms/kg) produced a dose-related inhibition of ejaculation but not significant inhibition of erection by the manual stimulation of the penis. Sperm was not found in the urine drawn from the urinary bladder, suggesting that the inhibitory effect of CL on ejaculation was not due to retrograde ejaculation. The ejaculatory disturbance elicited by CL (5 micrograms/kg) was antagonized by an alpha 2-adrenoceptor antagonist, yohimbine (1-10 micrograms/kg, i.c.v.) in a dose-related manner. In contrast to the effect of yohimbine, it was unaffected by an alpha 1-adrenoceptor antagonist, prazosin (3 and 10 micrograms/kg, i.c.v.). These results indicate that i.c.v. administered CL may selectively inhibit the ejaculatory response, which is presumably mediated through the stimulation of alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1986

[Effects of tooth pulp stimulation on single unit activity of the amygdala in cats].

Responses induced by tooth pulp stimulation were studied in 27 gallamine immobilized adult cats. Single units were recorded from the amygdala using stainless steel microelectrodes. Of 57 amygdaloid neurons, 8 were responsive to only non-nociceptive (tap and/or hair bending) stimuli, 7 were responsive to both nociceptive (pinch) and non-nociceptive stimuli, 18 were responsive to nociceptive stimuli, non-nociceptive stimuli and tooth pulp stimulation, and the others did not respond to these stimuli. The neurons in the amygdala responsive to tooth pulp stimulation were localized in the nucleus amygdaloideus centralis (pars lateralis) [Acl], nucleus amygdaloideus centralis (pars medialis) [Acl] and nucleus amygdaloideus basalis (pars magnocellularis) [Abm]. The response induced by tooth pulp stimulation was depressed by morphine and reversed by naloxone. These results suggest that Acl, Acm and Abm in the amygdala may receive pain sensation evoked by tooth pulp stimulation. Moreover, there is a possibility that these nuclei may be related to the emotional component involved in nociceptive processing.

Afferent Pathways↗
PubMed1986

Head-twitches induced by p-hydroxyamphetamine in mice.

Head-twitches have been regarded as an experimental model of hallucination, and we have recently observed that p-hydroxyamphetamine (p-OHA) markedly induced head-twitches in mice. The present work was undertaken to study possible participation of a serotonergic system in the mechanism of head-twitches induced by p-OHA. Head-twitches induced by p-OHA continued for 20-80 min, and the peak time of this effect was approximately 30-40 min after the administration. The i.c.v. administration of p-OHA (20, 40, 80 and 160 micrograms/mouse) produced characteristic head-twitches in a dose-dependent manner. Simultaneous injection of serotonin (10 micrograms/mouse, i.c.v.) and p-OHA caused a 2-2.5-fold increase in the number of head-twitches compared with non-serotonin controls. Pretreatment with p-chlorophenylalanine (200 mg/kg, i.p. and 500 micrograms/mouse, i.c.v.), in contrast, reduced head-twitches as did the pretreatment with cyproheptadine or dimethothiazine. These results suggest that p-OHA-induced head-twitches may involve the central serotonergic system which may exert an excitatory effect on head-twitches.

Amphetamines↗
PubMed1986

Studies on the hypothermic response of capsaicin and its analogue in mice.

Administration of capsaicin (CAP) and its related pungent, nonanoyl vanillylamide (NVA) produced significant dose-dependent hypothermic response in mice at an ambient temperature of 24 degrees C. CAP was approximately equieffective to NVA in producing hypothermia. After large doses, desensitization occurred to the hypothermic effects of both CAP and NVA. The hypothermia produced by CAP and NVA was prevented by a small dose of thyrotropin-releasing hormone (TRH) (0.25 nmol/animal) which by itself had little effect on body temperature. Histidyl-proline diketopiperazine, a metabolite of TRH, was without effect on the hypothermic response of CAP and NVA. The result suggests that a TRH neuronal system in the brain may explain a part of the mechanism of CAP- and NVA-induced hypothermia in mice.

Animals↗
PubMed1985

On the degradation of dermorphin and D-Arg2-dermorphin analogs by a soluble rat brain extract.

Degradation of dermorphin, [D-Arg2]dermorphin and [D-Arg2, Gly3, Phe4]dermorphin in a soluble rat brain extract was examined. The former two heptapeptides were degraded in a similar fashion to produce corresponding N-terminal tetrapeptide as the main degradation product along with the parallel release of Tyr5, Pro6 and Ser7-NH2. Tyr-D-Arg-Phe-Gly showed a good enzymatic stability. When captopril, an angiotensin-converting enzyme inhibitor, was present in the incubation mixture, hydrolysis of the Gly4-Tyr5 bond was markedly suppressed and resulted in release of the corresponding N-terminal hexapeptide as the main degradation product. Combined use of captopril and amastatin, an aminopeptidase inhibitor, markedly suppressed the hydrolysis of these peptides. On the other hand, [D-Arg2, Gly3, Phe4]dermorphin was hydrolyzed easier than the other two heptapeptides and considerable amounts of Tyr1 and Phe4 were released after 20 hr incubation while the N-terminal tetrapeptide, Tyr-D-Arg-Gly-Phe, showed a good enzymatic stability. On the basis of these results, possible degradation pathways of these heptapeptides were discussed.

Amino Acids↗
PubMed1985

The antinociceptive effects of histidyl-proline diketopiperazine and thyrotropin-releasing hormone in the mouse.

Intracerebroventricular (i.c.v.) injection of histidyl-proline diketopiperazine [cyclo (His-Pro)], an active metabolite of thyrotropin-releasing hormone (TRH) in mice produced an antinociceptive effect in a dose-dependent manner as measured in four antinociceptive tests; tail-pressure, tail-flick, hot-plate and acetic acid writhing. The antinociceptive effect of cyclo (His-Pro) reached a maximum at 5 min and lasted for 30 min. The ED50 values for the tests were 760.0 (598.4-965.2), 540.0 (442.6-658.8), 595.0 (487.7-725.9) and 370.0 (286.8-477.3) nmol/mouse and the slope functions were 1.61, 1.56, 1.57 and 1.66, respectively. Pretreatment with naloxone (0.5, 2 and 8 mg/kg), an opioid antagonist, administered subcutaneously antagonized the antinociceptive effect of cyclo (His-Pro). TRH injected i.c.v. to mice also exerted a dose-dependent antinociceptive action as measured in three antinociceptive tests; tail-pressure, hot-plate and acetic acid writhing. The antinociceptive effect of TRH was only seen at 5 min. The ED50 values for each test were 112.0 (47.5-264.3), 19.2 (10.4-35.5) and 0.2 (0.1-0.4) nmol/mouse and the slope functions were 8.89, 4.14 and 3.94, respectively. TRH was without effect in the tail-flick test. In contrast to cyclo (His-Pro), TRH-induced antinociception was not antagonized by pretreatment with naloxone (0.5, 2 and 8 mg/kg). The data suggest that the two peptides have a different mechanism of antinociceptive action in relation to the involvement of the opioid system in the central nervous system.

Acetates↗
PubMed1985

Intrathecal substance P analogue causes motor dysfunction in the rat.

(D-Pro2, Trp7,9)-substance P injected into the subarachnoid space produced a severe faccid extension of hindlimb in a dose-related manner in the rat. This motor dysfunction was neither reversed by naloxone, an opioid receptor antagonist nor by intrathecal SP. SP levels in the lumbar cord were markedly depleted in rats with hindlimb paralysis, though there was not significant changes in rats without paraplegia. These results suggest that DPDT-SP produces motor dysfunction which dose not appear to be mediated by opioid and SP receptors.

Animals↗
PubMed1985

Characterization of the hyperalgesic effect induced by intrathecal injection of substance P.

Substance P (SP) was administered to awake rats by injection into the lumbar subarachnoid space via an indwelling cannula. Intrathecal (i.t.) injection of substance P produced a dose-related hyperalgesic response in the tail-pressure assay. This hyperalgesic effect peaked at 1 min and returned to control level within 15 min. Tachyphylaxis to the action of substance P was not observed by successive intrathecal injections. The hyperalgesic effect induced by substance P was increased by pretreatment with naloxone and blocked by a large dose of morphine. A synthetic analogue (D-Pro2, D-Trp7,9)-substance P, was not found to block the action of substance P on mechanical responses. These results suggest that substance P apparently produces a direct action on spinal substance P receptors and the antagonistic effect of morphine on the hyperalgesia induced by substance P may be mediated through a postsynaptic mechanism in the spinal cord.

Animals↗
PubMed1985

Enhancement of phenol-induced tremor caused by central monoamine depletion.

The effects of monoamine depletors and monoamine denervators on phenol-induced tremor were studied in mice. The tremor induced by phenol was enhanced by pretreatment with reserpine or tetrabenazine, but not with syrosingopine. However, alpha-methyl-p-tyrosine, p-chlorophenylalanine or 6-hydroxydopamine did not affect the tremor. These results suggest that the depletion of central monoamines as a whole contribute to the enhancement of the tremor induced by phenol.

Animals↗
PubMed1985

The analgesic activity of D-Arg2-dermorphin and its N-terminal tetrapeptide analogs after subcutaneous administration in mice.

D-Arg2-dermorphin and its nineteen N-terminal tetrapeptide analogs were prepared, and their analgesic activities after subcutaneous administration in mice and the stability of a D-Arg2-dermorphin tetrapeptide to enzymatic degradation were examined. The analgesic effect was assessed by the tail pressure test. D-Arg2-dermorphin was found to have analgesic potency equal to or slightly greater than that of dermorphin. In a series of tetrapeptide analogs, a very pronounced activity greater than that of morphine was observed for analogs of the following structure, H-Tyr-D-Arg-Phe-X-OH (X = Gly, sarcosine and D-Ala) or its esters. Replacement of D-Arg2 by D-Arg(NO2), D-homoarginine or D-Lys resulted in a decrease in potency, suggesting that the guanidino group and side chain length of D-Arg2 are of great importance for a higher activity. D-Arg2-tetrapeptide (H-Tyr-D-Arg-Phe-Gly-OH) was found to be more stable than the parent tetrapeptide (H-Tyr-D-Ala-Phe-Gly-OH) to cleavage both by aminopeptidase M and by carboxypeptidase Y.

Analgesics, Opioid↗
PubMed1985

[Effects of serial administration of vanillyl n-nonoylamide on vocalization responses by arterial algogenics in guinea pigs].

Desensitizing effects of vanillyl n-nonoylamide, one of the synthetic capsaicinoids, were investigated by algogenics induced vocalization in conscious guinea pigs. Intra-arterial administration of bradykinin, acetylcholine and capsaicinoids (capsaicin, dihydrocapsaicin, vanillyl n-nonoylamide) evoked strong vocalization responses. Increasing doses (50 mg/kg, 100 mg/kg, 200 mg/kg, 400 mg/kg) of vanillyl n-nonoylamide were given to guinea pigs by subcutaneous administration for 4 days. Consecutive administration of vanillyl n-nonoylamide produced a weak but not significant desensitizing effect on bradykinin, acetylcholine-evoked vocalization at several doses. However, a complete suppressive effect on capsaicinoids-evoked response was observed in animals treated with serial administration of vanillyl n-nonoylamide. A weak vocalization response reappeared by three kinds of capsaicinoids (3 micrograms), but there were statistically significant effects on vocalization count when compared with the control values. It was therefore concluded that serial administration of vanillyl n-nonoylamide had a selective desensitizing action on chemonociceptors.

Acetylcholine↗