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Biomedical subjects

S Sakurada

Publications and source records attributed to S Sakurada.

At least 127 records · Page 7Linked to original sources
PubMed1990

Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice.

The effects of peptidase inhibitors were examined upon behavioural responses including scratch, bite and lick produced by intrathecal (IT) injection of substance P (SP) and neurokinin A (NK A) in mice. Phosphoramidon (0.002-2.0 nmol), an endopeptidase-24.11 inhibitor, simultaneously injected with SP or NK A, remarkably enhanced and prolonged SP- or NK A-induced behavioural response in a dose-dependent manner. The behavioural response to SP was significantly increased by 2.0 nmol of bestatin, an aminopeptidase inhibitor, but not by 1.0 nmol. Captopril, an angiotensin-converting enzyme inhibitor, was without effect on both tachykinin-induced responses. When phosphoramidon was injected together with bestatin and captopril which have no significant effect alone, SP- or NK A-induced behavioral response was significantly increased. These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level.

Aggression↗
PubMed1990

Monosodium urate test: a new analgesic test by crystal-induced monoarthritis in rats.

The analgesic effects of various agents were evaluated in knee joint monoarthritic rats where arthritis was induced by monosodium urate (MSU) crystals injected into the knee joint cavities. The weight supported by each hind limb was measured quantitatively using pressure transducers, which revealed dose-dependent recovery produced by various analgesics including morphine but no changes in value by sedatives such as chlorpromazine. Relative potency obtained from the value of ED50 of each analgesic agent was congruent with that in clinical use. The MSU test may be quite suitable for quantitative and objective evaluation of the analgesic effects of various agents, particularly for spontaneous and tonic pain.

Analgesia↗
PubMed1990

The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice.

1. Intrathecal (i.t.) administration of N-methyl-D-aspartate (NMDA) elicited a dose-dependent behavioural response consisting of licking, biting and scratching in mice. 2. Repeated i.t. injections of 0.4 nmol NMDA, at 5 min intervals, resulted in the rapid development of desensitization to this NMDA-induced behavioural phenomenon. 3. The NMDA-induced response was dose-dependently inhibited by the simultaneous injection of a selective NMDA-receptor antagonist, D-2-amino-5-phosphonovaleric acid. 4. The substance P (SP) analogues [D-Pro2, D-Trp7,9] SP and [D-Arg1, D-Trp7,9, Leu11] SP (spantide) inhibited NMDA-induced behavioural responses in a dose-dependent manner. However, [D-Phe7, D-His9] SP (6-11), a SP analogue selective for neurokinin1 (NK1) receptors, failed to inhibit NMDA-induced responses even at a dose of 4.0 nmol. 5. These results indicate that NMDA-induced behavioural responses are mainly mediated through NMDA receptors without affecting NK1 receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗
PubMed1990

Different profile of electrocortical power spectrum changes after micro-infusion into the locus coeruleus of selective agonists at various opioid receptor subtypes in rats.

1. The effects of various opioid receptor agonists given directly by means of a chronically implanted cannula into the locus coeruleus (LC) on behaviour and ECoG activity, continuously analysed, and quantified as total power spectrum (0-16 Hz) and in preselected frequency bands (0-3; 3-6; 6-9; 9-12 and 12-16 Hz), were studied in rats. 2. Dermorphin (0.05, 0.5, 1, 2 and 5 pmol) and Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO; 1, 10, 30, 100 pmol and 1 nmol), two typical mu-receptor agonists, applied unilaterally or bilaterally directly into the LC, produced a typical dose-dependent ECoG synchronization with a significant increase in total power spectrum as well as in the lower frequency bands. Dermorphin was found to be approximately 30 times more powerful than DAMGO in producing similar quantitative ECoG changes. 3. D-Ala-D-Leu-Thr-Gly-Gly-Phe-Leu (DADLE; 1, 10, 50 and 100 pmol), a selective delta-receptor agonist, micro-infused into the LC produced dose-dependent behavioural soporific effects and ECoG increase in total power spectrum as well as in 3-6, 6-9, 9-12 Hz frequency bands. In comparison to dermorphin, the ECoG power spectrum effects of DADLE were 10 fold less potent, whereas in comparison to DAMGO it was approximately 3 times more potent. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 4. The microinfusion into the LC of U 50, 488H, a selective Kappa-opioid receptor agonist, (0.25, 1, 2.5, 5 and lOpmol) produced a typical pattern characterized by a first short-lasting (3-25 min) phase of behavioural arousal and ECoG desynchronization, followed by a longer lasting (20-130min according to the dose) phase of behavioural sleep and ECoG synchronization. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 5. Dextromethorphan and ketamine, two selective agonists at sigma-receptors given into the LC (1, 5 and 1Opmol) induce behavioural arousal, increase in locomotor activity and an intense pattern of stereotypedm movements. However, by increasing the dose of ketamine (50 and lOOpmol), marked sedation, postural changes and an increase in low frequency ECoG bands, sometimes associated with high amplitude fast frequency potentials, were observed. 6. Naloxone applied directly into the LC (1 and 2 pmol 15min before) was able to prevent the behavioural and ECoG effects induced by dermorphin, DAMGO and DADLE. Higher doses of naloxone (1Opmol into the LC) were however, required to antagonize the behavioural and ECoG soporific effects induced by the Kappa-receptor agonist U 50,488H. In contrast, naloxone (1Opmol into the LC) was unable to prevent or reduce the behavioural and ECoG effects induced by subsequent administration into the same site of dextromethorphan and ketamine. 7. In conclusion, the present experiments confirm that behavioural and ECoG effects elicited following stimulation of mu-, delta-, Kappa- and sigma-opioid receptors located in the LC are quite different. Activation of ,mu-, band Kappa-receptors induced sedative effects whereas dextromethorphan and ketamine, two sigma-receptor agonists, induced behavioural arousal and ECoG desynchronization. In addition, the present results strongly support the crucial role played by opioid mechanisms, in the locus coeruleus, in the mediation of the soporific effects of drugs acting as agonists at opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Substance P analogues containing D-histidine antagonize the behavioural effects of intrathecally co-administered substance P in mice.

The antagonistic effect of newly synthesized substance P (SP) analogues containing D-histidine was examined on behavioural responses induced in mice by SP, neurokinin (NK) A, physalaemin, eledoisin, somatostatin and bombesin. [D-Pro2,D-Trp7,9]SP (DPDT-SP) and [D-Arg1,D-Trp7,9,Leu11]SP (spantide) were used as references for comparison. When co-administered with SP intrathecally, all the SP analogues used decreased the SP-induced response which consists of scratching, biting and licking. DPDT-SP and spantide attenuated non-specifically the SP-like behavioural responses induced by physalaemin, eledoisin, NK A and somatostatin. In general, the introduction of D-histidine in position 9 of the SP molecule resulted in potent antagonistic activity of the SP derivative on the behavioural responses to SP. Of these SP analogues, [D-Arg1,D-Pro2,4,D-Phe7,D-His9]SP attenuated selectively the behavioural responses produced by NK-1 receptor agonists such as SP and physalaemin. Simultaneous injection of [D-Phe7,D-His9]SP-(6-11) selectively inhibited the SP-induced behavioural response without affecting the other peptide-induced behavioral response. The results suggest that the behavioural antagonism induced by [D-Arg1,D-Pro2,4,D-Phe7,D-His9]SP and [D-Phe7,D-His9]SP-(6-11) is probably due to the specific blockade of spinal NK-1 receptors.

Amino Acid Sequence↗
PubMed1989

Beta-interferon and early stage HIV infection.

beta-Interferon (IFN-beta) was evaluated prospectively for its antiviral activities in early stage human immunodeficiency virus (HIV) infection. Ten patients with hemophilia and HIV infection [8 asymptomatic carriers (AC) and 2 AIDS-related complex (ARC)] were intravenously injected with 1 million IU of IFN-beta twice a week for 6 months. For comparison, seven patients (six AC and one ARC) with hemophilia and HIV infection were observed for the same time period without any drugs. One episode of localized herpes zoster each occurred during the trial in the IFN group and in the control group. There were no significant differences in the absolute number of CD4+ lymphocytes and ratios of CD4+/CD8+ lymphocytes between the two groups. Recipients had flu-like symptoms but no serious toxicities. No clinical and immunological benefits to patients with early stage HIV infection were observed during the 6 months of treatment.

Acquired Immunodeficiency Syndrome↗
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↗
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

Electrocortical spectrum power effects of different classes of neuroleptics in rats.

In freely moving rats the effects on behaviour and ECoG spectrum power of different classes of neuroleptics (phenothiazines, butyrophenones and benzamides) after systemic and intraventricular administration were studied. Chlorpromazine and haloperidol given systemically or microinjected into the third cerebral ventricle produced behavioural and ECoG slow-wave sleep (SWS) accompanied by a significant increase in ECoG total voltage power as well as in the lower frequency bands; haloperidol was found to be more powerful in inducing behavioural and SWS. In contrast, equimolar doses of 1-sulpiride given systemically or higher doses microinjected into the third cerebral ventricle did not produce significant behavioural and ECoG changes. Thus, the present experiments confirm that neuroleptic drugs may possess a different ECoG profile depending on their structure and provide further evidence concerning the role played by dopaminergic mechanisms in the control of sleep-arousal.

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

Behavioural and electrocortical changes induced by muscimol in rats withdrawn from chronic treatment with diazepam.

In rats withdrawn from a chronic treatment with diazepam, the effects of muscimol, given into the III cerebral ventricle, on behaviour and spectrum power of activity in the electrocorticogram (ECoG) were studied. In comparison to control rats which received only muscimol, in rats pretreated with diazepam (1 mg/kg/day for 30 consecutive days) the behavioural and ECoG effects of muscimol were significantly reduced or abolished. In fact, in rats pretreated with diazepam a small dose (50 ng) of muscimol did not affect behaviour or ECoG activity, in contrast to control animals in which the same dose produced, after a period of locomotor stimulation and ECoG desynchronization, typical and long-lasting behavioural sedation or sleep accompanied by a significant increase in total voltage power and in the lower frequency bands in the ECoG. In addition, larger doses (100 and 200 ng) of muscimol, which in control rats produced a typical biphasic pattern of ECoG and behavioural changes, i.e. an initial period of ECoG desynchronization and behavioural stimulation, followed by a second period of behavioural and ECoG sleep, in animals pretreated with diazepam, produced only an increase in total voltage power and in the lower frequency bands in the ECoG resembling the effects of the smaller (50 ng) dose. The present experiments suggest that, after chronic stimulation of benzodiazepine receptors a decrease in sensitivity of receptors for gamma-aminobutyric acid (GABA) occurs, since the effects of muscimol on behaviour and spectrum power were significantly reduced or abolished.

Animals↗
PubMed1987

Behavioural and ECoG spectrum power effects after intraventricular injection of drugs altering dopaminergic transmission in rats.

In rats with cannulae permanently implanted into the third cerebral ventricle, the effects of different pharmacological manipulations affecting dopaminergic mechanisms, were studied on behaviour and electrocorticographic (ECoG) activity, continuously quantified in its spectrum power. The intraventricular injection (0.1-1 nmol) of (-)3PPP[3-(3-hydroxyphenyl) N-n-propylpiperidine], a specific agonist at dopamine (DA) autoreceptors, produced dose-dependent behavioural sedation or sleep and an increase in ECoG spectrum power, with a predominant increase in the lower frequency bands. Short episodes of stereotyped movements, wet-dog syndrome, penile grooming and erection were also observed. Similar behavioural and ECoG effects were elicited by the intraventricular injection of R-(+)-8-chloro-2,3,4,5-tetrohydro-3-methyl-5-phenyl-1H-3-benzazepi ne-7-ol (SCH 23390), a selective antagonist at D1 postsynaptic receptors, although these were preceded by a short period of behavioural and sexual stimulation. In addition, the intraventricular administration of some neuroleptics, chloropromazine and haloperidol, produced behavioural and ECoG slow wave sleep. No significant changes were observed with a neuroleptic drug, 1-sulpiride, which is reputed to act selectively as an antagonist at dopamine D2 receptors. In conclusion, the present experiments add new evidence in favour of the idea that dopaminergic mechanisms are involved in mammalian species in the control of arousal and that both post-synaptic D1 and D2 receptors may take part in such a control.

Animals↗