PubMed Health⌕ Search

Biomedical subjects

R Inoki

Publications and source records attributed to R Inoki.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effect of neurotropin on hyperalgesia induced by prostaglandin E2, naloxone, melatonin and dark condition in mice.

Subcutaneous injection of formaldehyde into mouse hind paw elicited pain responses consisting of licking or biting of the paw, which were observed biphasically. The first and second phases were enhanced by melatonin and melatonin, naloxone, prostaglandin E2, respectively. Mice kept in the dark also exhibited hyperalgesic response. When neurotropin was injected intraperitoneally 30 min prior to those treatments, hyperalgesia was suppressed to the control level. Aspirin inhibited only the second hyperalgesic phase.

Analgesics↗
PubMed1987

Positive inotropic action of kappa opiate agonists, ethylketocyclazocine and dynorphin-A(1-13), in isolated rat atrium.

The effect of various opiate agonists on the contraction of isolated rat atrium was investigated. Ethylketocyclazocine (EKC) (30-100 microM) and dynorphin-A(1-13) (10-30 microM), which are kappa-type agonists, caused positive inotropic effects on electrically stimulated left atrium in a dose-dependent manner. In addition, EKC decreased the frequency of spontaneous beating in the right atrium. Morphine (mu-type), [Met5]- and [Leu5]-enkephalin (delta-type) did not affect both the developed tension and frequency of contractions. These results indicate that the positive inotropic action is specific for kappa-type opiate agonists.

Animals↗
PubMed1987

Contribution of substance P to heat-induced edema in rat paw.

To investigate a physiological function of substance P (SP) present in the peripheral ending of sensory neurons, we determined immunoreactive SP (iSP) levels in the s.c. perfusate and the amount of edema evoked in rat paw by noxious heat stimulation. We found that immersion of rat paw into hot water (47 degrees C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in paw volume. Neonatal pretreatment with capsaicin inhibited significantly the increase in both iSP and paw volume evoked by noxious heat stimulation. Acute and chronic denervation of the sciatic and saphenous nerves also inhibited the heat-evoked iSP release and edema remarkably. Intraplantar injection of SP evoked an increase in paw volume in dose-dependent manner. This increasing effect of SP on paw volume was more substantial than that produced by histamine. Simultaneous treatment with stem bromelain and emorfazone decreased significantly the heat-evoked iSP release and edema. These results suggest that 1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers with small-diameter, 2) bradykinin may intervene in this SP release and 3) SP released in the periphery may be closely related to the edema formation of the thermal injury reaction.

Animals↗
PubMed1986

Effects of opioids and opioid peptide on the release of substance P-like material induced by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit.

The superficial layer in subnucleus caudalis of the brain-stem trigeminal sensory nuclear complex (SpVc) in the rabbit was perfused with artificial cerebrospinal fluid using a push-pull perfusion cannula system. Immunoreactive substance P (iSP) and [Met5]enkephalin (iME) released into the perfusates following electrical stimulation of the lower incisor pulp were measured. An increase in the release of iSP and iME lasting for 1 h or more was observed following electrical stimulation with 40 V. The increase in iSP release depended on the intensity of stimulation. Systemic morphine (10 mg/kg i.v.) completely inhibited the stimulus-evoked iSP release and this inhibition was antagonized by pretreatment with naloxone (5 mg/kg i.v.). The stimulus-evoked iSP release was also inhibited by local application of morphine (10(-6) M) or the opioid peptide [D-Ala2,Met5]enkephalinamide (10(-4) M). However, the local application of naloxone (5 X 10(-7) M) only partially antagonized the inhibitory effects of locally applied morphine and the opioid peptide. These results suggest that there is a functional interaction between SP and enkephalin systems in the superficial layer of SpVc for the regulation of dental pain transmission.

Animals↗
PubMed1986

Stereospecific effects of d- and l-pentazocine on contractions of the mouse vas deferens.

The effects of the d- and l-isomers of pentazocine were compared to that of racemic pentazocine on contractions of the mouse isolated vas deferens. L-pentazocine inhibited electrically evoked contractions of the mouse vas deferens (MVD) in a dose-dependent manner (ID50 0.37 +/- 0.04 microM). In contrast, d-pentazocine augmented field stimulated contractions dose-dependently; per cent increases in contractions at 10 and 30 microM were 57.8 +/- 18.0 and 98.0 +/- 15.1%, respectively. Racemic pentazocine produced an intermediate effect between the two isomers. The effect of 1-pentazocine was antagonized by naloxone, whereas that of d-pentazocine was not. L-pentazocine did not effect the response of the MVD to exogenous norepinephrine at any concentration tested, while d-pentazocine depressed the response of the MVD to exogenous norepinephrine at one dose (0.3 microM). These findings demonstrate that d- and l-pentazocine produce opposite effects on the MVD. The effects of l-pentazocine are opioid mediated, while those of d-pentazocine are not. In the racemic mixture the opposing effects of the two isomers modulate each other, resulting in a diminished effect.

Animals↗
PubMed1986

[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system].

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.

Analgesics↗
PubMed1986

[Peripheral analgesic actions of opioid peptides and morphine analogues].

Opiates and opioid peptides were administered in the order of 10(-9)-10(-6) mol peripherally, and their action on pain sensitivity was investigated by the modified formalin test which has two characteristic pain responses (the first and the second phase) in the mouse hindpaw. Opioid peptides (20-500 pmol) had dose-dependent analgesia against both first and second phases, and their action ranked dynorphin greater than [D-Ala2, Met5]-enkephalinamide greater than [Met5]-enkephalin. EKC and morphine (0.4-2.5 nmol) inhibited pain response of the first phase, but produced hyperalgesia in the second phase dose-dependently. Lidocaine hydrochloride had peripheral analgesic action, but was about 500-10000 times weaker than these substances. So, these peripheral analgesic actions have a different mechanism from that of local anesthetic action. N-methyl levallorphan which is thought to be a peripherally selective narcotic antagonist reversed these peripheral analgesic actions at the first and second phases and also prevented the hyperalgesic effects of EKC and morphine at the second phase. Naloxone reversed analgesia at only the first phase. These results suggest that an analgesic mechanism by opioids may exist at the peripheral site as well. Furthermore, it is estimated that a receptor exists which is antagonized by N-methyl levallorphan but not by naloxone and that there is a system of hyperalgesia by EKC and morphine in pain modulation.

Analgesics, Opioid↗
PubMed1986

Effects of noxious stimuli and anesthetic agents on substance P content in rat central nervous system.

Effects of noxious electrical tooth stimulations and intraarterial administration of bradykinin or inhalation of volatile anesthetics on substance P content in the diencephalon-mesencephalon, pons-medulla and the spinal cord were examined in the rat. Noxious stimulation by electrical long duration stimulation (type 2) of tooth pulp caused an increase of substance P content in the ponsmedulla. Inhalation of volatile anesthetics such as methoxyflurane and diethylether produced an increase of substance P content in the spinal cord; and in addition, methoxyflurane produced a decrease of substance P content in ponsmedulla. However, halothane did not produce any changes in substance P content in any parts of the central nervous system (CNS). These results suggest that volatile anesthetics such as diethyl-ether and methoxyflurane act on the substance P neuron and may modulate pain transmission through the action of substance P in the pons-medulla or the spinal cord.

Anesthetics↗
PubMed1986

Interaction of bradykinin with substance P on vascular permeability and pain response.

Combination of bradykinin with substance P exerted synergistic effects on vascular permeability and pain response in mouse paw. Denervation of sciatic nerve reduced significantly bradykinin-induced vascular permeability, suggesting the involvement of sensory nerves. The bradykinin-induced vascular permeability was also reduced by intravenous injection of a substance P-antagonist. The results suggest that neuronal substance P takes part in the action of bradykinin on inflammation and pain sensation.

Animals↗
PubMed1986

Participation of opiate and serotonergic systems in brain conditioning stimulatory inhibition of the potentials evoked by tooth pulp stimulation in the pars caudalis of the trigeminal sensory nucleus of the rat.

Effects of conditioning stimulations of the nucleus raphe magnus (NRM), nucleus reticularis paragigantocellularis (NRPG), mesencephalic periaqueductal central gray (PAG), nucleus dorsomedialis hypothalami (DMH), corpus striatum (CP), sensory cortex (SCT) and visual cortex (VCT) and actions of morphine, naloxone and metergoline on the potentials recorded from the pars caudalis of the trigeminal sensory nucleus evoked by the electrical stimulation of rat incisor pulps were examined. The spinal potentials evoked by electrical stimulation of the pulp consisted of 3 components. Component 2 was mainly inhibited by morphine and antagonized by naloxone. Conditioning stimulation of NRM, NRPG, PAG, CP, SCT and DMH strongly inhibited component 2. VCT did not show any inhibition. 33-67% of antagonism was observed by naloxone in the NRM, NRPG, PAG, CP, SCT and DMH. On the other hand, 27-44% of antagonism was observed by metergoline, and the antagonism was not enhanced by the additional administration of naloxone. These results conclusively show that the endorphin system as well as the serotonergic system is in the series involved in the descending inhibition for nociception in the trigeminal sensory nucleus.

Animals↗
PubMed1986

Distribution of enkephalin-like immunoreactivity in the feline heart; its interrelation with substance P- and vasoactive intestinal polypeptide-like immunoreactive nerve fibers.

Distribution of enkephalin (Enk)-like immunoreactivity in the feline heart was investigated by indirect immunofluorescence method. Enk-like immunoreactive (Enk-IR) nerve fibers and cells predominated in the atria but were rare in the ventricles. Enk-IR cells were mainly distributed near sinoatrial (SA) node and between aorta and pulmonary artery. These cells were usually grouped in clusters near blood vessels or cardiac ganglia. Some Enk-IR cells appeared to extend their processes to other Enk-IR cells, cardiac ganglia, blood vessels and rarely cardiac muscles in the atria. Furthermore, substance P (SP)- and vasoactive intestinal polypeptide (VIP)-IR nerve fibers were closely associated with some Enk-IR cells. Moreover, the distribution and morphological profiles of Enk-IR cells were very similar to those of catecholamine (CA)-containing cells.

Animals↗
PubMed1986

Influence of Y-20003, an analgesic agent, on the endogenous opioid peptide system in rats.

Changes of endogenous opioid peptide system by pain stimuli were examined using adjuvant-induced arthritic rats. Following the 5th day after adjuvant inoculation, met-enkephalin (ME)-like peptide content in plasma decreased, while after the 12th day, the peptide content increased in adrenal medulla. A significant correlationship was found between pain threshold and plasma ME-like peptide content. Y-20003, a new nonsteroidal agent without inhibition of prostaglandin biosynthesis, showed an analgesic effect which was significantly antagonized by naloxone or Win 44,441-3, suggesting that endogenous opioid peptide system may be involved in the analgesic mechanism of Y-20003.

Adrenal Medulla↗
PubMed1984

Effects of morphine and (D-Ala, Met)-enkephalinamide on 45Ca-uptake to rat brain striatal slices.

Effects of morphine and (D-Ala, Met)-enkephalinamide on 45Ca-uptake to rat striatal slices were examined. While morphine didn't give any effect on 45Ca-uptake to striatal slices in normal Krebs-Ringer solution, it inhibited K+ (40 mM)-stimulated 45Ca-uptake to slices. In high K+ medium, 45Ca-uptake was enhanced to 170% and this was reduced to 147 and 137% by 10(-5) and 10(-4) M morphine, respectively. Furthermore, the effect of morphine was antagonized by 10(-5) M naloxone. (D-Ala, Met)-enkephalinamide (10(-4) M) also inhibited K+-stimulated 45Ca-uptake to the slices to the same extent as was observed by morphine. K+-stimulated 45Ca-uptake to striatal slices obtained from chronically morphine administered rat (6 mg/kg, twice/day, 7 days) was not inhibited by morphine.

Animals↗
PubMed1984

Effect of neuroactive peptides on labeled 5-hydroxytryptamine release from rat spinal slices in vitro.

Effects of neuroactive peptides on the release of labeled 5-hydroxytryptamine (5-HT) from preloaded rat spinal cord slices were investigated. The 5-HT release was significantly stimulated by somatostatin (10-50 microM) and substance P (10-50 microM), but not by neurotensin (50 microM), beta-endorphin (30 microM) and methionine-enkephalin (met-enk) (100 microM). Somatostatin-stimulated 5-HT release was markedly inhibited by gamma-aminobutyric acid (GABA) (30 microM), but not by baclofen (30 microM) and met-enk (100 microM). Substance P-stimulated 5-HT release was strongly inhibited by GABA (30 microM) and baclofen (30 microM), but not by met-enk (100 microM). High concentrations (20 mM) of potassium also stimulated 5-HT release. The high potassium-stimulated 5-HT release was not affected by GABA (30 microM) and met-enk (100 microM). These results suggested further evidence on the important role of somatostatin and substance P as modulators of serotonergic neurones.

Animals↗
PubMed1983

Effect of inhalational anesthetics on the opioid receptors in the rat brain.

Effects of inhalational anesthetics, methoxyflurane and halothane, on the binding of various opioid ligands were studied. The binding affinity of 3H-methionine enkephalin (delta) was reduced by both anesthetics in the same manner, but the receptor density was not significantly affected. Methoxyflurane decreased the binding affinity but increased the receptor density of 3H-dihydromorphine (mu), while halothane had little effects on both affinity and density. Methoxyflurane also decreased binding affinities of 3H-ethylketocyclazocine (kappa) and 3H-SKF-10047 (sigma), but halothane did not decrease significantly. These effects of the anesthetics were completely disappeared by unsealing and ventilation.

Animals↗