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Biomedical subjects

N Yonehara

Publications and source records attributed to N Yonehara.

54 records · Page 3Linked to original sources
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↗
PubMed1984

Effects of delta and mu opiopeptides on the turnover and release of dopamine in rat striatum.

Two mu and two delta opiopeptides were administered intracisternally and morphine was administered systemically to rats. The level of dopamine (DA) and its catabolites, homovanillic acid, dihydroxyphenylacetic acid and 3-methoxytramine were measured by high-pressure liquid chromatography with electrical detector in rat striatum to determine: 1) whether opioids alter the release of DA from striatal neuron (which would be indicated by changes in the level of 3-methoxytramine, the extraneuronal catabolite) and 2) whether delta or mu ligands have a greater effect on DA turnover. We found that the levels of 3-methoxytramine did not rise in response to the administration of any opiopeptide or morphine. However, mu opiopeptides produced a small but significant decrease in these levels, indicating that there was no increase, but instead a slight decrease in DA release. The delta opiopeptides produced larger increases in homovanillic acid and dihydroxyphenylacetic acid than the mu ligands, indicating that delta ligands are more effective on an equidose basis in increasing the turnover of striatal DA. The opiopeptides were also tested for pharmacological activity at the same dose (3 micrograms/rat). All four peptides were effective in reducing locomotor activity and producing analgesia. One peptide, Tyr-d-Ala-Gly-N-Mephe-Met-O-ol, also produced catalepsy. There was no segregation of these two behavioral responses according to ligand specificity. Morphine acted like a delta ligand in affecting DA turnover.

Animals↗
PubMed1983

Is a calmodulin-opiopeptide interaction related to the mechanism of opioid action?

The effect of several opioids: methadone, etorphine, beta-endorphin and D-ala2met enkephalin on Ca++/calmodulin stimulation of enzyme activities either in pure solution (cyclic nucleotide phosphodiesterase) or in striatal membranes (protein kinases in synaptic membranes) were compared to see if a direct opioid/calmodulin interaction could eliminate the stimulation of enzyme activity as part of the mechanism by which opioids alter ion flow and neurotransmitter release. In other experiments, in which endogenous phosphorylation of proteins in striatal synaptic membranes was altered by opioid treatments, the possibility of restoring protein kinase activity to normal levels in the membrane preparation by supplementation with calmodulin at optimal Ca++ concentration was examined. Some opioids (methadone and D-ala2met enkephalin) did not inhibit calmodulin-stimulated phosphodiesterase, which suggests that they were not able to bind to calmodulin. In addition, it was not possible to restore decreases in protein kinase activity to normal levels by adding calmodulin to the assay in the presence of optimal Ca++. We conclude that a direct binding of opioids to calmodulin is not a general mechanism of opioid action, although the binding may participate in the action of some neuropeptides, including beta-endorphin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Algesiogenic and analgesic activities of synthetic substance P.

The objective of our study was to determine whether the pure synthetic substance P(SP) is algesiogenic or analgesic when administered centrally or peripherally. The relationships between SP-induced analgesia and the content of morphine-like factor (MLF) in the brain were also studied. Intracarotid arterial administration of SP (20-200 microgram) produced no pseudoaffective responses to pain in six out of nine rats, but in the remaining three, there was an exhibition of these responses. Chlorpheniramine pretreatment antagonized these responses. On cantharidin blister base experiments in humans, SP (10(-3) g/ml) produced slight pain and an itchy sensation. SP given intracerebroventricularly produced an analgesia in mice in a dose of 5 ng/mouse, as determined by the acetic acid-induced writhing and hot plate methods. These SP-induced analgesia were antagonized by naloxone pretreatment. SP did not alter the content of MLF in the mouse whole brain. However, SP5-11 not only produced an analgesia but also increased the content of MLF. These results suggest that SP has a slight algesiogenic activity which might be mediated by histamine and a slight analgesic activity which might be mediated by MLF.

Analgesics↗
PubMed1980

Inhibitory effect of dibutyryl cyclic GMP on potassium-stimulated 45Ca uptake by synaptosomes from rat brain.

The effects of dibutyrl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by the P2 fraction of Gray and Whittaker were investigated with the following results. (1) db-cGMP inhibited the initial rate of potassium-stimulated 45Ca-uptake in a dose-dependent manner in 0.1 mM Ca0 medium, but had no effect on the uptake in low K+ medium. In 0.1 mM Ca0 medium, the concentration of db-cGMP causing 50% inhibition was about 3 mM. db-cAMP (5 mM) had no effect on the uptake. (2) db-cGMP-inhibited potassium-stimulated 45Ca uptake in 1 mM Ca0 medium, though less than in 0.1 mM Ca0 medium. (3) db-cGMP inhibited potassium-stimulated 45Ca uptake by synaptosomes (pinched-off nerve terminals) more than the uptakes by other subfractions of P2 fraction. It is suggested from the results that cGMP inhibits the Ca influx resulting from depolarization of the nerve endings in situ.

Animals↗
PubMed1980

Effect of cyclic nucleotide derivatives on the release of ACh from cortical slices of the rat brain.

Atropine (5 nM to 5 muM), but not D-tubocurarine or hexamethonium, enhanced the release of acetylcholine (ACh) from rat brain cortical slices exposed to high K+. The enhancement was dose-dependent, and it could be partially antagonized by oxotremorine (50-500 muM) or by dibutyryl or 8-bromo-cyclic GMP (1 mM), but not by tetrodotoxin (200 nM) or by dibutyryl cyclic AMP (1 mM). The effects of oxotremorine and the cyclic GMP derivatives were not due to diminished ACh synthesis, since these compounds did not influence the reduction of tissue ACh resulting from treatment with K+ and atropine. These results suggest that cyclic GMP may mediate the regulation of ACh release by presynaptic muscarinic receptors.

Acetylcholine↗
PubMed1979

Subcellular ascorbic acid in scorbutic guinea pig brain.

In scorbutic guinea pigs fed an ascorbic acid-deficient diet for 18 days, the ascorbic acid contents of the liver and plasma were less than 4% those of the control animals, while the content in the brain was about one-third that of the controls. In normal animals, the concentration of ascrobic acid was highest (7.55 +/- 1.46 micrograms of ascorbic acid/mg protein) in the S3 fraction and was also fairly high (5.37 +/- 0.91) in the P2p fraction (cytoplasm of nerve terminals). During ascorbic acid deficiency, the contents in the P2p and microsome fractions decreased slightly faster than those in other fractions. Even after 18 days' deficiency, no significant change was found in the acetylcholine content of the brain.

Acetylcholine↗