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Biomedical subjects

R Inoki

Publications and source records attributed to R Inoki.

At least 37 records · Page 2Linked to original sources
PubMed1990

[Stabilizing effect of prostaglandin E2 on lysosomal membrane of the rat dental pulp].

It has been reported that prostaglandin E2 (PGE2) had anti-inflammatory and analgesic effects, although it was well known that PGE2 combined with bradykinin (BK) showed proinflammatory and algesic effects. On the other hand, it has recently been known that BK showed an indirect activating effect on cathepsin B, a lysosomal enzyme, which may be mediated through calcium ion-dependent steps, followed by production of enkephalins (EK), endogenous anti-inflammatory and analgesic peptides, in the rat incisor pulp. The purpose of the present study is to examine whether PGE2 could have an effect on activation or release of cathepsin B in the pulp tissue, or not. Intact whole pulps of the rat incisors were incubated with N alpha-benzoyl-arginine-beta-naphthylamide (BANA), a substrate for cathepsin B, in the presence or absence of BK and PGE2 in Hanks solution (pH 7.4), in order to determine the BANA-degrading activity and EK producing activity. Both hydrocortisone and lidocaine which were stabilizers for lysosomal membrane markedly inhibited the BANA-degrading activities in the presence of BK, and in contrast, retinol, a labilizer for lysosomal membrane, significantly enhanced the BK-induced BANA-degrading activity. PGE2, like hydrocortisone and lidocaine, inhibited the BANA-degrading activity, in a dose-dependent manner, regardless of the presence or absence of BK, as well as resulted in a decrease of EK production in the pulp. Furthermore, both arginine, a cleavage product of BK by carboxypeptidase B, and arachidonic acid, which were endogenous activators for soluble guanylate cyclase, enhanced the BANA-degrading activity in the pulp homogenate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of pentazocine and other opioids on the potassium-evoked release of [3H]noradrenaline from guinea pig cortical slices.

Noradrenaline release and its modulation via presynaptic opioid receptors were examined in guinea pig cortical slices. Slices preloaded with [3H]noradrenaline were superfused in the presence of desipramine (1 microM) and were stimulated by 16 mM K+. 1-Pentazocine inhibited the K+-evoked release of [3H]noradrenaline in a dose-dependent manner (3 x 10(-7)-10(-5) M), while d-pentazocine did not inhibit. This inhibitory effect of 1-pentazocine was antagonized by Mr 2266 (10(-6) M) but not by naloxone (10(-6) M). Among other opioids, dynorphin A-(1-13) and ethylketocyclazocine (kappa agonists) decreased the K+-evoked release of [3H]noradrenaline. Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO, mu agonist) also inhibited [3H]noradrenaline release but was less potent than the kappa agonists. [D-Pen2,D-Pen5]enkephalin (DPDPE, delta agonist) and phencyclidine (sigma agonist) had no effects on the stimulated release of [3H]noradrenaline. Thus, it was shown that kappa receptors are the major subtype of opioid receptor involved in modulation of noradrenaline release in guinea pig cortex, and that 1-pentazocine inhibits the K+-evoked release of noradrenaline through activation of these receptors.

Animals↗
PubMed1989

Activation of calcium ion-dependent proteinases by bradykinin in dental pulp of the rat.

The present study was aimed to examine whether BANA-degrading enzyme activities could be enhanced by bradykinin(BK) in dental pulp of the rat in vitro. The results showed that BK(0.1-10 microM) dose-dependently enhanced BANA-degrading enzyme activity at pH 7.4. The effects of BK(1 microM) were found to be most effective at both pH 7 and 8, with enhancement of the enzyme activities at a wide range of pH. The BK effects at both the pH were not inhibited by FOY-305(0.1 microM), an inhibitor of trypsin-like enzymes, differing from that at pH 6 in adrenal medulla of the rat. On the other hand, the effects of BK at both the pH were remarkably inhibited by EGTA (2 mM), followed by reversal with calcium ion (2.42 mM). These results suggested as follows: 1) there might be two kinds of BANA-degrading enzymes activated by BK in the pulp. 2) it was conceivable that BANA-degrading enzymes activated by BK were quite different from serine proteinases and were interfered with them in the pulp. 3) calcium ion might play a role in BK-induced enhancement of BANA-degrading enzyme activities which were regarded as met-enkephalin (ME) processing enzyme activities in the pulp.

Animals↗
PubMed1989

Enhancement of proteinase activities by bradykinin in adrenal medulla of the rat.

In the present study, a significant positive correlationship was found between the contents of bradykinin (BK)-like and met-enkephalin(ME)-like peptides in adrenal medulla of the rat with cavity-formed incisors in vivo, and the production of ME-like peptides was increased by BK in adrenal medulla of the rat in vitro. Influence of BK on the degradation of BANA, a synthetic substrate for trypsin, by the tissue enzymes was also studied. It was found that BK (0.1-10 microM) enhanced the enzyme activities in a dose-dependent manner, and the effect of BK(1 microM) was most effective at pH 6 and 8. The BK effect was inhibited by FOY-305, an inhibitor of serine proteinases, at pH 6, but not at pH 8. However, E-64, an inhibitor of cysteine proteinases, reduced the BK effects at both pH 6 and 8. These results suggested that 1) BK was an activator for BANA-degrading enzymes which were thought as processing proteinases of ME-like peptides in adrenal medulla of the rat, and 2) there may be, at least, two kinds of BANA-degrading enzymes activated by BK, one might be a serine proteinase with optimal pH at 6, and the others might be cysteine proteinases with optimal pH at both 6 and 8.

Adrenal Medulla↗
PubMed1989

Changes in [3H]nitrendipine binding and gamma-aminobutyric acid release in rat hippocampus following repeated morphine administration.

An antagonistic effect of calcium on the action of morphine was studied in rat hippocampal slices. The effect of repeated administration of morphine on gamma-aminobutyric acid (GABA) release and binding of [3H]nitrendipine, a calcium antagonist, was also examined. (1) In rat brain hippocampal slices, morphine enlarged the amplitude of the field potentials evoked in pyramidal neurons, disinhibiting them through basket cells. When the calcium concentration was elevated, potentiation of the field potentials by morphine was reduced. Decrease of the calcium concentration, on the other hand, enhanced the potentiating effect of morphine. Following repeated administration of morphine, its enhancing effect on the field potentials in slices was not observed. (2) In hippocampal membrane fractions obtained from rats repeatedly treated with morphine, enhancement of [3H]nitrendipine binding was observed. (3) In hippocampal slice preparations from rats receiving morphine repeatedly, K+ (45 mM)-stimulated [3H]GABA efflux was enhanced. The above results indicate that morphine antagonizes calcium, thereby reducing the release of transmitters. Furthermore, increase in calcium channels following repeated treatment of rats with morphine may explain the mechanism underlying development of tolerance.

Action Potentials↗
PubMed1989

Further evidence for possible analgesic mechanism of electroacupuncture: effects on neuropeptides and serotonergic neurons in rat spinal cord.

The possible mechanism of electroacupuncture (EAc) in reference to the effects of neuropeptides on serotonergic neurons in rat spinal cord was studied. The tested drugs were administered by intrathecal injection or spinal push-pull perfusion. The results showed that baclofen, substance P (SP) and naloxone administered intrathecally could reduce the tail pressure pain threshold. The pain threshold was increased by met-enkephalin (EK) and EAc. The action of EAc was antagonized by naloxone. The release of 5-HT in the spinal cord evoked by tail pressure pain stimulation (TP) was inhibited by EK, baclofen and EAc. However, naloxone could potentiate the 5-HT release evoked by TP. EAc reversed the naloxone potentiation of TP-evoked 5-HT release. The 5-HT release evoked by exogenous SP, however, was potentiated by EK and EAc. From these results, it is suggested that the influence of EAc on 5-HT release may be due to activation of enkephalin-interneurons, which presynaptically inhibit the primary sensory neurons in the spinal cord.

Acupuncture Therapy↗
PubMed1989

Distribution of substance P and methionine-enkephalin in salivary glands and effect of chronic morphine treatment on levels of these peptides.

Substance P-like immunoreactivity (SPLI) and methionine-enkephalin-like immunoreactivity (MELI) were determined in salivary glands from rats by radioimmunoassay. In all salivary glands investigated (submandibular gland, sublingual gland and parotid gland), SPLI and MELI were detected. The amount of both peptides is comparable to or relatively higher than those found in any other peripheral tissue. The level of SPLI showed a tendency to increase following chronic treatment with morphine: the enhancement in the submandibular gland and the sublingual gland was especially remarkable. The level of MELI was decreased, particularly in the submandibular gland.

Animals↗
PubMed1989

Effects of d- and l-pentazocine on the release and uptake of norepinephrine in rat brain cortex.

Effects of d- and l-pentazocine on the release and uptake of norepinephrine and other neurotransmitters were examined in rat cerebral cortex. D- and l-pentazocine (10(-6)-10(-4) M) evoked the release of tritium from rat cortex slices preloaded with [3H]norepinephrine. Both isomers of pentazocine (3 x 10(-5) M) also evoked the release of tritium from slices preloaded with [3H]dopamine and [3H]5-hydroxytryptamine ([3H]5-HT) but did not from those preloaded with [3H] gamma-aminobutyric acid ([3H]GABA) and [3H]choline. The releasing effect of pentazocine was neither dependent on the extracellular calcium nor antagonized by naloxone. Both isomers inhibited the uptake of [3H]norepinephrine, [3H]dopamine and [3H]5-HT but not that of [3H]GABA and [3H]choline into synaptosomes prepared from the cortex. These results suggest that the effects of d- and l-pentazocine on release and uptake are relatively specific to monoamines and might explain some aspects of pharmacological actions of pentazocine.

Animals↗
PubMed1989

[Interaction between bradykinin and enkephalins in rat dental pulp].

The content of bradykinin (BK)-like peptides in rat dental pulp was significantly increased 1, 6 and 24 h after cavity formation at the neck of incisor. We have reported that enkephalin (EK)-like peptides in rat dental pulp were increased by cavity formation or BK. In the present study, the mechanism of the production of EK enhanced by BK was investigated using benzoyl-L-arginine-2-naphthylamide (BANA), a synthetic substrate. BK and its products cleft by carboxypeptidase B, des-Arg9-BK and arginine (Arg), activated the degradation of BANA. It is suggested that these substances may enhance the processing of enkephalins from precursor proteins. The activating effects were inhibited by EGTA. The BANA-degrading enzymes in lysosomal fraction were activated by BK, des-Arg9-BK and Arg, but the enzymes in supernatant were activated by Arg only. On the other hand, morphine and met-EK inhibited the production of BK-like peptides by trypsin from plasma kininogen. It is suggested that BK is cleft by carboxypeptidase B in pulp cell to des-Arg9-BK and Arg, which activate the lysosomal or soluble EK processing enzymes, and then the produced EK inhibits the production of BK from plasma kininogens in the pulp.

Animals↗
PubMed1988

Decrease in analgesic effect of nifedipine following chronic morphine administration.

The analgesic effect of nifedipine, a calcium antagonist, was compared in the acetic acid-induced writhing test with control and morphine-tolerant mice. Nifedipine inhibited the writhing syndrome less effectively in mice made tolerant to morphine. The results support the notion that inhibition of the calcium influx is one of the causes of the analgesic action of morphine and that its chronic administration causes an increase of calcium entry.

Acetates↗
PubMed1988

Release of inflammatory mediators by noxious stimuli; effect of neurotropin on the release.

Anesthetized rats were perfused with saline in the subcutaneous space of the hind paw and the release of inflammatory mediators induced by noxious stimuli was studied. Not only immunoreactive bradykinin (BK) but also histamine, serotonin (5-HT) and immunoreactive prostaglandin E2 (PGE2) were found to be released into the perfusate when the paw was pinched. Neurotropin, used clinically as an analgesic and anti-allergic drug in Japan, inhibited the release of BK in dose-dependent manner without altering the release of histamine, 5-HT and PGE2. The maximal inhibition of BK release was observed 60 min after p.o. administration of neurotropin. Indomethacin failed to inhibit the release of BK.

Animals↗
PubMed1988

Effects of opioids on the heat stimulus-evoked substance P release and thermal edema in the rat hind paw.

We examined the effect of opioids on the heat stimulus-evoked release of substance P (SP) into the subcutaneous space and the formation of edema in the rat hind paw. Immersion of the rat hind paw for 30 min into hot water adjusted to 47 degrees C led to a marked increase in the release of SP into the subcutaneous perfusate with the formation of thermal edema. Intra-arterial infusion of morphine (10-100 mumol/kg) or ethylketocyclazocine (30-100 mumol/kg) inhibited dose dependently the heat stimulus-evoked increase in SP release and the thermal edema and the inhibitory effects were antagonized by pretreatment with N-methyl levallorphan (10 mg/kg i.p.) and Win 44,441-3 (10 mg/kg i.p.). The heat stimulus-evoked release of SP was reduced significantly during the intra-arterial infusion of [D-Ala2,Met5] enkephalinamide (100 mumol/kg). These results suggest that the opioid-induced inhibition of heat-induced edema could result from inhibition of the release of SP from peripheral sensory nerve endings.

Animals↗
PubMed1988

Inhibition of cardiac Na+, K+-ATPase activity by dynorphin-A and ethylketocyclazocine.

The effect of various opioids on Na+, K+ -ATPase partially purified from rat heart was examined. Dynorphin-A (1-13), dynorphin-A (1-17) and ethylketocyclazocine (EKC), which are k-type opiate agonists, markedly inhibited the enzyme activity in a dose-dependent manner; IC50 values were 12 microM, 21 microM and 0.38 mM, respectively. Morphine (mu-type agonist), methionine- and leucine-enkephalin (delta-type agonist) at the concentration of 1 mM did not affect the enzyme activity. The effect of dynorphin-A (1-13) and EKC was not antagonized by naloxone. Dynorphin-A (1-13) mainly decreased Vmax value without the change of Km value in the activation of Na+, K+-ATPase by ATP, Na+ and K+. Dynorphin-A(1-13) inhibited the partial reactions of Na+, K+-ATPase at the different degree of the potency; the inhibition of K+-stimulated phosphatase was greater than that of Na+-dependent phosphorylation. The present study suggests that dynorphin-A and EKC have an effect on cardiovascular system which is mediated by the inhibition of Na+, K+-ATPase in the heart.

Adenosine Triphosphate↗
PubMed1988

Occurrence of methionine-enkephalin-like immunoreactive cells in the feline vagus nerve.

The occurrence of peptidergic cellular elements in the feline vagus nerve was examined by an immunohistochemical method. Some methionine-enkephalin-like immunoreactive cells were present around a few capillaries within the vagus nerve, whereas substance-P- and vasoactive-intestinal-polypeptide-like immunoreactive cells were not observed. The methionine-enkephalin-like immunoreactive cells had an oval shape and their diameter was 7-10 micron. These cells appeared to be in contact with the pericyte of the capillaries. Though the physiological function of these enkephalin-positive cells is unclear, our findings suggest that they can act as endocrine cells and release methionine-enkephalin into the capillaries.

Animals↗
PubMed1988

Stimulation of phospholipase A2 and vascular permeability by an extract of granuloma induced in the rat by carrageenin.

Isolation from carrageenin-induced granuloma of rat of factors affecting phospholipase A2 (PLase A2) activity was attempted. Excised granuloma was extracted with 2% phenol and denatured both at acidic and alkaline pH's in boiling water. The extract was adsorbed on charcoal and eluted in an alkaline milieu. Following gel chromatography of the eluate on Sephadex G-25, the effect of this fraction on PLase A2 prepared from rabbit peritoneal exudates was examined. Materials affecting PLase A2 activity were eluted slightly behind the peak of saccharides having an approximate molecular weight of 800. Activation of PLase A2 was most pronouncedly observed in the sample prepared from 5 days granuloma. Activating effect on PLase A2 was not observed with the sample prepared from control rat skin. The effect of fractions that contained PLase A2 activating components on vascular permeability was investigated by measuring the leakage of i.v. administered pontamine blue. Injection of the sample containing PLase A2-activating materials into mouse paw induced the increase of vascular permeability in a dose dependent manner. Maximal effect was observed also in the sample obtained 5 days after the injection of carrageenin. Thus, the activating components may be involved in the processes of inflammation.

Animals↗