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K Kisara

Publications and source records attributed to K Kisara.

At least 109 records · Page 6Linked to original sources
PubMed1988

Substance P(1-7) antagonizes substance P-induced aversive behaviour in mice.

Substance P (SP) and its fragments were administered intrathecally into awake mice. SP and C-terminal fragments caused dose-dependent reciprocal hindlimb scratching responses. SP(5-11) was more potent than SP not only in inducing scratching response but also in inducing aversive behaviour including licking and biting. SP(1-7) induced no behavioural reactions. However, when low doses of SP(1-7) (1.0-4.0 pmol) were injected simultaneously with SP or SP(5-11) (0.1 nmol), aversive behaviours induced by SP or SP(5-11) were significantly reduced. These results indicate that SP(1-7) formed endogenously could modulate the actions of SP or SP(5-11) in the spinal cord.

Animals↗
PubMed1988

Enkephalins interact with substance P-induced aversive behaviour in mice.

The effect of the endogenous opioid peptides, methionine-enkephalin (Met-ENK), beta-endorphin (beta-END) and dynorphin-(1-17) (DYN) on the aversive behavior produced by intrathecal (i.t.) administration of substance P (SP) was studied in mice. A low dose of i.t. administered Met-ENK gave a marked reduction of the SP-induced response. In the tail-flick assay, such doses of Met-ENK were ineffective in producing antinociception. At much higher doses, however, Met-ENK obtained antinociceptive activity. In contrast, beta-END and DYN had about the same potency in inhibiting the SP-induced behavioural response and in the tail-flick test, respectively. These results suggest that opioid peptides, particularly enkephalin neurons in the spinal cord influence SP-induced aversive behaviour.

Animals↗
PubMed1988

Comparison of the antinociceptive effects of new [D-Arg2]-dermorphin tetrapeptide analogs and morphine in mice.

The antinociceptive effects of synthetic dermorphin tetrapeptide analogs containing D-Arg in position 2, H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH, were measured in mice by the tail-pressure test. The antinociceptive effect produced by intracerebroventricular (ICV), intrathecal (IT) and subcutaneous (SC) administration of either peptide was greater than that produced by morphine. Oral (PO) administration of the peptides showed approximately the same antinociceptive potency as morphine. In addition, the antinociceptive effect produced by SC and PO administration of either peptide was of longer duration than morphine. Pretreatment with naloxone resulted in nearly complete antagonism of the antinociceptive effects produced by ICV and IT administration of either peptide or morphine. Dose ratios (ICV/IT) of H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH, which were calculated from the AD50 (Antinociceptive Dose = 50% MPE) values, were 5.8 and 6.2, respectively, whereas that of morphine was only 1.46. These results suggest that the mechanisms of the antinociceptive effects of [D-Arg2]-dermorphin tetrapeptide analogs differ from morphine, and that these peptides may possess higher affinities than does morphine for opioid receptors in the spinal cord.

Analgesics, Opioid↗
PubMed1988

Antinociception and physical dependence produced by [D-Arg2] dermorphin tetrapeptide analogues and morphine in rats.

1. The antinociceptive effects of [D-Arg2] dermorphin tetrapeptide analogues, H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH when administered subcutaneously (s.c.) in rats were measured by the tail-flick test. In addition, the appearance of typical withdrawal signs upon cessation of administration or on subsequent treatment with naloxone were measured after chronic administration of either peptide or morphine. 2. The dose of peptides and of morphine in the physical dependence test was determined from the AD50 to inhibit the tail-flick test in rats. Doses from 4 to 64 times the AD50 doses were employed in the s.c. administration schedules. 3. The intensity of the antinociception induced by either peptide was greater than that produced by morphine. Moreover, the antinociception induced by the peptides was of much longer duration than that produced by morphine. 4. Abrupt withdrawal after chronic administration of either peptide produced only slight loss of body weight. In contrast, morphine withdrawal produced sharp loss of body weight. 5. Naloxone precipitated withdrawal signs after chronic administration of either peptide were less intense than those after chronic morphine. 6. These results suggest that the antinociception produced by these peptides is more intense and of longer duration than that produced by morphine. It is also interesting to note that the physical dependence produced by these peptides is less marked than that produced by morphine.

Analgesics↗
PubMed1988

[Effect of cysteamine on vocalization responses by arterial algogenics in guinea pigs].

Effects of cysteamine (2-mercaptoethylamine) on vocalization responses, a parameter of nociceptive response, was studied in conscious guinea pigs. Intra-arterial injection of bradykinin (3 micrograms), acetylcholine (300 micrograms), capsaicin (3 micrograms) and vanillyl n-nonoylamide (3 micrograms, VNA) induced severe vocalization responses. Three hours after an administration of cysteamine (300 mg/kg, s.c.), a significant suppressive effect was observed for bradykinin and acetylcholine-evoked vocalization. A weak suppressive effect appeared in capsaicin and VNA-evoked vocalization, but there were not statistically significant changes on vocalization counts when compared with the value of the saline-treated animals. However, consecutive pretreatment of guinea pigs with VNA led to a complete suppression of capsaicinoids-evoked vocalization only. Cysteamine completely suppressed bradykinin, acetylcholine, capsaicin and VNA-evoked vocalization responses in VNA desensitized guinea pigs. These findings suggest that the mechanisms of bradykinin and acetylcholine-evoked vocalization response differ from that of capsaicinoids.

Acetylcholine↗
PubMed1988

Studies on 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine: determination of the MAO-A or MAO-B selective inhibition in vitro.

To further clarify highly MAO-A- or -B-selective inhibitory properties of 5-fluoro-alpha-methyltryptamine (5-FMT) and p-chloro-beta-methylphenethylamine (p-CMPEA), we determined the types and K1 values of inhibition of rat brain MAO-A and -B activity in vitro. The kinetic data obtained showed that 5-FMT is a competitive MAO-A-selective inhibitor with about a 18,000-fold higher sensitivity than MAO-B. In contrast, p-CMPEA is a competitive MAO-B-selective inhibitor with about a 620-fold higher sensitivity. Based on the present findings of highly MAO-A- or -B-selective inhibition, these two compounds might prove to be of value in in vivo studies.

Amphetamines↗
PubMed1987

Acute effects of a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mouse body temperature.

The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in single systemic doses (i.p.) to mice produced marked hyperthermia, and subsequent long-lasting hypothermia. Administration of MPTP or its oxidized product, 1-methyl-4-phenylpyridinium ion, MPP+, via i.c.v. resulted in only hypothermia. In contrast, i.p. MPP+ administration resulted in only hyperthermia. The MPTP-induced hyperthermia (i.p.) was blocked by quaternary derivatives of anti-cholinergic agents, atropine and scopolamine, but not by the tertiary-derivative of atropine. Duration of this hyperthermic effect was potentiated by neostigmine. Pretreatment with 1-deprenyl did not prevent hypothermia, but nomifensine partially or clorgyline completely prevented the effect without preventing MPTP-induced hyperthermia. The thermic effects by MPTP, unlike its neurotoxicity for the nigrostriatal DA system, may not require metabolism to MPP+. These results indicate that peripheral cholinergic functions are responsible for the MPTP-induced hyperthermia, whereas its hypothermic effect may be centrally mediated via dysregulation of the various neuron systems.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Central hypothermic effects of some analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+).

Effects of some MPTP or MPP+ analogues on mouse body temperature were studied. Of the analogues tested, 4-phenylpyridine (PPY) and 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) given in single i.p. doses to mice caused marked hypothermia. Intracerebroventricular (i.c.v.) injection of PPY or PTP caused similar hypothermia. Pretreatment with clorgyline or (-)-deprenyl greatly prevented hypothermia induced by i.c.v. PPY, but hypothermia by i.c.v. PTP was prevented only by (-)-deprenyl. These results indicate that, in order to cause central hypothermia, PTP does not seem to require metabolism to PPY and both analogues per se may cause hypothermia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Behavioral and biochemical changes following acute administration of MPTP and MPP+.

The acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on mouse locomotor activity and striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were investigated. A single dose of either MPTP (10-30 mg/kg, i.p.) or MPP+ (5-20 ug/mouse, i.c.v.) decreased locomotor activity 10-40 min after injection: this locomotor effect was significantly suppressed by either pretreatment with nomifensine or 1-deprenyl alone, or by the combination of desmethylimipramine and 6-hydroxydopamine. Pretreatment with clorgyline did not suppress this behavior and a single dose of haloperidol enhanced the effect. The striatal levels of DA, 3-methoxytyramine and 5-HT increased in parallel with the decrease in locomotor activity caused by MPTP or MPP+. In contrast, levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were decreased by injection of either MPTP or MPP+. Possible mechanism(s) of the behavioral and biochemical changes caused by the acute actions of MPTP and MPP+ with respect to their neurotoxic effects on the nigrostriatal DA system are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Behavioural effects of intrathecally injected tachykinins in rats with peripheral nerve transection.

The effect of unilateral sciatic nerve transection on behavioural responses produced by intrathecal administration of substance P (SP), neurokinin A, eledoisin and physalaemin was investigated in the rat. The injection of SP (3 nmol/rat) into the subarachnoid space was followed by reciprocal scratching, biting and licking of the fore- and hind-limbs. There was no observable difference in the behavioural response to SP between rats with nerve transection and sham operated rats at 5 days after operation. Whereas at 10, 20, and 30 days after nerve transection the response to SP was significantly increased as compared with sham operated rats. This phenomenon was also observed with neurokinin A (1.5, 3.0 and 6.0 nmol/rat), eledoisin (0.05 and 0.10 nmol/rat) and physalaemin (0.05 and 0.10 nmol/rat) at 10 days after operation. Ipsilateral depletion of SP from the lumbar (L4-L6) spinal cord was observed at 5, 10, 20, and 30 days after the unilateral transection of the sciatic nerve. These results suggest that sciatic nerve transection may produce an increased response to tachykinins through an enhanced sensitivity of tachykinin receptors in the lumbar cord.

Animals↗
PubMed1987

Behavioural characterization of substance P-induced nociceptive response in mice.

Intrathecal injection of substance P produced a behavioural syndrome, consisting of reciproacal hindlimb scratching and biting or fore- and hind-licking. Pretreatment with either an analogue of substance P, (D-Pro2, D-Trp7,9)-substance P (DPDT-SP) or (D-Arg1, D-Pro2,4, D-Trp7,9, Leu11)-substance P, given intrathecally, reduced the response to substance P in a dose-dependent manner. The behaviour induced by substance P was also inhibited by intrathecal, intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of morphine. Intrathecal or subcutaneous injection of naloxone showed a biphasic effect on substance P response; the substance P-induced nociceptive response was increased by a small dose of naloxone, while it was inversely decreased by a large dose of naloxone. The results with analogues of substance P support the hypothesis that substance P, injected intrathecally, acts directly on substance P receptors in the spinal cord. The nociceptive response induced by substance P appears to be controlled by endogenous opioids in the spinal cord.

Animals↗
PubMed1987

Involvement of alpha-adrenoceptors in para-hydroxyamphetamine-induced head-twitch response.

The effect of some drugs with a higher selectivity for either the alpha 1- or alpha 2-adrenoceptors on the head-twitches induced by intracerebroventricular administration of p-hydroxyamphetamine (p-OHA) in mice, have been studied. Pretreatment with yohimbine increased the number of head-twitches induced by p-OHA, whereas pretreatment with clonidine or prazosin reduced the number of responses. The decrease in head-twitches produced by clonidine was completely antagonized by pretreatment with yohimbine. Pretreatment with 6-hydroxydopamine prior to the combined treatment with clonidine and p-OHA, resulted in recovery of the reduced level head-twitches to the level induced by p-OHA alone. Pretreatment with 6-hydroxydopamine alone resulted in a marked increase in the number of p-OHA-induced head-twitches. These results clearly indicate that a noradrenaline system in the brain may, at least in part, be involved in the p-OHA-induced head-twitches in mouse, most probably by modulating a serotonergic system which is responsible for the head-twitch response.

Amphetamines↗
PubMed1987

Suppressive effects of intraventricular injected dopamine and nomifensine on muricide induced by thiamine deficiency.

The effects of dopamine (DA) and nomifensine (NF) on muricide activity induced by thiamine deficiency were examined. The chronic administration of L-dopa and nomifensine during feeding of thiamine deficient diet attenuated the muricide activity. Moreover, acute administration of L-dopa or nomifensine (IP) and dopamine or nomifensine (ICV) suppressed the thiamine deficiency-induced muricide activity dose-dependently. Small doses of apomorphine inhibited the muricide response significantly. The suppressive effects of dopamine and nomifensine were antagonized by pretreatment with 6-hydroxydopamine, but were not changed by pretreatment with p-chlorophenylalanine. These results suggest that the dopaminergic system has an important role in the regulation to the thiamine deficiency-induced muricide response.

Aggression↗
PubMed1987

Behavioural assessment as substance P antagonists in mice.

A series of eleven undeca- and four hexapeptide antagonists of substance P (SP) have been assayed by the SP-induced behavioural test in mice. When 2 nmol of [D-Arg1, D-Pro, D-Trp, Leu]-SP (SP 1-11 I) was intrathecally injected together with SP (0.1 nmol), SP-induced response which consists of scratching, biting and licking was markedly inhibited. [D-Trp, Leu]-SP 6-11 (SP 6-11 I) given in a dose of 2 nmol was also inhibited the SP-induced response to the same degree as SP 1-11 I. Some of SP 1-11 or SP 6-11 analogues substituted with fluorine in positions 7 and/or 8 maintained the antagonistic effect of SP 1-11 I or SP 6-11 I, though the others were weaker. Intrathecal administration of SP 1-11 I and SP 6-11 I resulted in long-lasting antinociceptive effects as measured by the tail-flick test. Fluorine-containing SP analogues were less potent than the above two analogues in producing antinociception. These results suggest that the antagonistic effect of SP analogues on the SP-induced nociceptive response do not necessarily relate to antinociceptive activity at the spinal cord level.

Analgesia↗
PubMed1987

[Effects of capsaicin on spontaneous unit discharges in amygdala single neurons of cats].

Effects of capsaicin on spontaneous unit discharges in the amygdala single neurons were studied in 26 gallamine immobilized adult cats. Single units were recorded from the amygdala using a stainless steel microelectrode. Of 63 amygdala neurons, 34 were responsive to both noxious (pinching the skin with toothed forceps) and innoxious (tap and/or hair bending) stimuli, 11 were responsive to only innoxious stimuli and the others did not respond to these stimuli. Of 34 neurons responsive to both noxious and innoxious stimuli, 20 were responsive to both bradykinin and capsaicin, and 7 were responsive to only capsaicin. All neurons responsive to bradykinin were also responsive to capsaicin. All neurons responsive to only innoxious stimuli responded to neither bradykinin nor capsaicin. The latency for bradykinin and capsaicin was 8.05 +/- 0.92 sec and 1.21 +/- 0.33 sec, respectively. The duration for bradykinin and capsaicin was 14.72 +/- 1.78 sec and 26.22 +/- 4.16 sec, respectively. The increase in firing frequency produced by capsaicin was depressed by morphine (1 mg/kg, i.v.). These depressant effects of morphine on the amygdala neurons were antagonized by naloxone (0.2 mg/kg, i.v.).

Action Potentials↗
PubMed1987

[The effect of nonanoyl vanillylamide on the chemically-induced nociception].

The aim of the present investigation was to determine the effects of a single dose and serial doses of nonanoyl vanillylamide (NVA) administered subcutaneously on responses induced by chemical stimuli in the mouse. The treatment with a single subcutaneous injection produced a significant decrease in the number of abdominal contraction responses produced by intraperitoneal injections of phenylbenzoquinone and in the responsive time of licking induced by plantar injection of formalin. The serial subcutaneous administration of NVA caused a dose related antinociceptive effect against a chemical nociceptive stimulus using the phenylbenzoquinone-induced writhing test, while NVA was ineffective against a chemical stimulus, formalin. These results suggest that serial doses of NVA administered peripherally cause different effects in two types of chemically-induced nociception.

Analgesics↗
PubMed1987

Opioid activities of D-Arg2-substituted tetrapeptides.

The antinociceptive effects and mechanisms of action of H-Tyr-D-Ala-Phe-Gly-OH, H-Tyr-D-Arg-Phe-Gly-OH and H-Tyr-D-Arg-Phe-sarcosine(Sar)-OH have been investigated. The ED50 values of these peptides were 510.0, 8.2 and 2.0 pmol, respectively, when administered i.c.v. in the mouse tail-pressure test (dermorphin = 5.7 pmol and morphine = 1.2 nmol). These activities were remarkably potent and relatively long lasting. Their IC50 values were 676.8, 23.1 and 6.6 nM, respectively (dermorphin = 3.75 and morphine = 214.3 nM) in the guinea pig isolated ileum assay, and 138.50, 5.25 and 1.10 nM, respectively (dermorphin = 3.80 and morphine = 28.00 nM) in the radioreceptor assay utilizing [3H]naloxone as the opioid receptor ligand. In the evaluation of their inhibitory effects to enkephalin-degrading enzymes, the IC50 values of H-Tyr-D-Arg-Phe-Gly-OH, H-Tyr-D-Arg-Phe-Sar-OH and H-Tyr-D-Ala-Phe-Gly-OH were 5.4, 14.5 and more than 50.0 microM, respectively (bestatin = 0.1 microM) against aminopeptidase and 1.18, 1.40 and more than 50.0 microM, respectively (captopril = 0.38 and D-Phe-2S-, 3R-3-amino-2-hydroxy-4-phenylbutanoic acid = more than 100 microM) against the cleaving enzymes of enkephalin at its Gly3-Phe4 bond. The authors suggest that the marked antinociceptive potency of H-Tyr-D-Arg-Phe-Gly-OH and H-Tyr-D-Arg-Phe-Sar-OH is mainly due to high opioid receptor affinity. Their inhibitory effects on enkephalin-degrading enzymes and enzymatic stability also greatly contribute to their potent and long-lasting opioid activities.

Animals↗