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N Yonehara

Publications and source records attributed to N Yonehara.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Releases of bradykinin and substance P by heating hind paw of rat].

Contribution of kallikrein-kinin system to heat-induced substance P (SP) release into the periphery was studied by using plasma kininogens-deficient strain Brown Norway Katholiek (B/N-Ka) and normal strain Brown Norway Kitasato (B/N-Ki) rats. Bradykinin (BK) and SP levels in the sc perfusates of the hind instep were measured by radioimmunoassay. In B/N-Ki rat, immersion of hind paw into hot water (47 degrees C) for 20 min led to an increase of BK (43 +/- s 34 fmol.min-1) and SP (11.1 +/- 9.7 fmol.min-1) in the perfusate, whereas those in B/N-Ka rat (BK 1.3 +/- 1.0 fmol.min-1 (P < 0.01), SP 5.5 +/- 3.5 fmol.min-1 (P < 0.05)) were remarkably less. Heat-induced extravasation (leakage of Evans blue) in B/N-Ka rat was also less than that in B/N-Ki rat (P < 0.05). Results suggest that kallikrein-kinin system is involved in the release of SP into the periphery, ie, BK released into the extravascular space by noxious heat stimulation intervenes in SP release.

Animals↗
PubMed1993

Opioid peptide release evoked by noxious stimulation of the hind instep of rats.

Previous studies showed that opioids and opioid peptides modulate vascular reactions such as plasma extravasation and vasodilatation through inhibition of substance P release from peripheral nerve endings of primary afferent fibers, and suggested the existence of endogenous opioid peptide activity related to regulation of inflammatory responses. Here we examined the effect of heat stimulation and antidromic stimulation of primary afferent fibers on the release of immunoreactive opioid peptides into the perfusate of the subcutaneous space in the rat instep. Antidromic stimulation of sectioned sciatic and saphenous nerves did not have any significant effect on the release of Met-enkephalin (Met-EK), while immersion of the hind paw in hot water (47 degrees C) for 30 min caused an increase in Met-EK release into the perfusate. High-pressure liquid chromatography of the perfusate revealed that noxious heat stimulation induced increase in release of Leu-enkephalin (Leu-EK) as well as Met-EK, although the maximal concentration of Leu-EK was less than 16% of that of Met-EK. No beta-endorphin was detected in the perfusate before, during or after heating. We conclude that noxious heat stimulation mainly leads to increase in Met-EK, and that this peptide originates mainly, from peripheral cells containing opioid peptides such as immune cells and/or Merkel cells, not from primary afferent fibers.

Animals↗
PubMed1993

Effect of morphine on changes in cutaneous blood flow induced by antidromic stimulation of primary afferent fibers in the hind instep of rats.

The effects of morphine on the release of immunoreactive substance P (iSP) into the subcutaneous perfusate and the changes in cutaneous blood flow (CBF) elicited by antidromic stimulation of sectioned sciatic nerve were investigated in the instep of the hind paw of rats. Antidromic stimulation of the sectioned sciatic nerve induced a marked increase in iSP release into the subcutaneous perfusate and a biphasic flow response consisting of an initial transient decrease followed by an increase. Both the iSP release and the increase of the CBF evoked by antidromic stimulation (the second phase) were significantly inhibited by intra-arterial (i.a.) infusion of morphine (30 mumol/kg). These inhibitory effects of morphine were antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The i.a. infusion of SP (0.25 mumol/kg) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. Neither phase induced by i.a. infusion of SP was affected by preinfusion of morphine (10 or 30 mumol/kg, i.a.). We suggest that morphine applied locally mainly acts on the peripheral endings of small-diameter afferent fibers, not on blood vessels, and that activation of this site is involved in the regulation of the microcirculatory hemodynamics of cutaneous tissue through inhibition of SP release.

Animals↗
PubMed1992

Influence of electro-acupuncture on the release of substance P and the potential evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit.

The effects of electro-acupuncture (EAP) on the release of substance P (SP) and the responses evoked by tooth pulp stimulation (ST) in superficial layers of the trigeminal nucleus caudalis (Vc-I,II) were studied in rabbits. ST evoked increase in release of immunoreactive SP (iSP). This increase was inhibited by EAP in 9 of 13 animals. The potentials evoked by ST were composed of two main components with latency times of ca 4.3 msec and ca. 9.4 msec. The latter component, reflecting the excitation of A delta fibers, was significantly inhibited by CP-96,345 (3 mg/kg, i.v.), an SP antagonist. EAP also inhibited the latter component in 8 of 11 animals. These results suggest that one of the mechanisms of analgesia induced by EAP is inhibition of stimulus-evoked SP release in the Vc-I,II.

Animals↗
PubMed1992

Influence of opioids on substance P release evoked by antidromic stimulation of primary afferent fibers in the hind instep of rats.

The effect of opioids on the release of immunoreactive substance P (iSP) following simultaneous electrical stimulation of the sectioned sciatic and saphenous nerves was examined by perfusion of the subcutaneous space in the rat instep. Antidromic stimulation of both the nerves caused an increase in iSP release, which was dependent on the intensity of stimulation, and an approx. 200% increase in Evans blue extravasation. Stimulation-induced iSP release and extravasation were suppressed by pretreatment with capsaicin (50 mg/kg s.c.) and spantide (10 mumol/kg i.p.), respectively. Intra-arterial infusion of morphine (30 mumol/kg) or ethylketocyclazocine (30 mumol/kg) or [D-Ala2,D-Leu5]enkephalin (30 mumol/kg) inhibited the increase in iSP release evoked by antidromic stimulation at 10 V. This inhibitory effect of morphine was antagonized by pretreatment with naloxone (2 mg/kg, i.p.). These results suggest existence of multiple types of opioid receptor on the peripheral endings of primary afferent fibers, that regulate SP release from the peripheral nerve endings into the extravascular space.

Afferent Pathways↗
PubMed1992

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.7. We suggest that SP and its receptors are mainly responsible for the vascular response induced by stimulation of the sectioned sciatic nerve, and that small-diameter afferent fibres containing SP tonically regulate vascular tone in cutaneous microvessels.

Animals↗
PubMed1991

Serotonin inhibits release of substance P evoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbits.

The influence of the serotonin (5-HT) system on the release of immunoreactive substance P after electrical stimulation of the lower incisor pulp was examined by perfusion of the superficial layers of the subnucleus caudalis of the brain stem trigeminal sensory nuclear complex of rabbits in situ. Increased release of immunoreactive substance P was observed after electrical stimulation of the pulp at 40 V. Stimulation of the nucleus raphe magnus significantly increased the release of 5-HT and completely inhibited the release of immunoreactive substance P, evoked by stimulation of the tooth pulp. Local application of 5-HT (10(-6) M) inhibited the release of immunoreactive substance P induced by stimulation and this inhibition was antagonized by methysergide (10(-4) M) applied concomitantly to the superficial layers of the trigeminal nucleus. These results suggest a functional interaction between substance P and 5-HT in the superficial layers of the trigeminal nucleus for regulation of transmission of dental pain.

Animals↗
PubMed1991

Influence of heat stimulation on the amount of calcitonin gene-related peptide and neurokinin A in the subcutaneous space of the rat hind instep.

The release of tachykinins and calcitonin gene-related peptide (CGRP) into subcutaneous perfusates was investigated. Immersion of the hind paw of rats in water at 47 degrees C for 30 min led to a marked increase of immunoreactive CGRP (iCGRP) release as well as immunoreactive substance P release, but no detectable increase of immunoreactive neurokinin A release. Neonatal pretreatment with capsaicin or section of the sciatic and the saphenous nerves significantly inhibited the heat stimulation-induced release of iCGRP.

Animals↗
PubMed1991

[Effects of morphine on cutaneous blood flow and substance P release evoked by electric stimulation of rat sciatic nerve].

Electric stimulation of the rat sciatic nerve containing sensory afferent fibers produced an increase in cutaneous blood flow. Morphine (10, 30 mumol.kg-1 ia infusion) inhibited the electric stimulation-induced increase of the cutaneous blood flow velocity, and its effect was antagonized by naloxone (2 mg.kg-1 ip). In order to investigate the cause of this effect, we determined immunoreactive substance P (iSP) levels in the sc perfusate of hind paw. We found that electric stimulation of the sciatic nerve led to a significant increase of iSP release into the sc perfusate. Morphine (30 mumol.kg-1 ia infusion) inhibited the electrical stimulation-induced release of iSP, and this effect was completely antagonized by naloxone (2 mg.kg-1 ip). These result suggest that morphine-induced inhibition of the electrical stimulation-evoked increase in cutaneous blood flow could result from inhibition of the release of SP from peripheral sensory nerve endings.

Animals↗
PubMed1990

Aversive taste stimuli increase CGRP levels in the gustatory insular cortex of the rat.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was surveyed immunohistochemically in the insular cortex of the rat, and the levels of insular cortical CGRP-IR were measured with the radioimmunoassay method following intraoral stimulation with various taste stimuli. CGRP-IR was localized in nerve fibers within the agranular and dysgranular insular cortices. The CGRP-IR levels in the rostral (gustatory) part of the insular cortex were increased significantly by strongly aversive taste stimuli such as quinine hydrochloride and conditioned taste stimuli (NaCl and sucrose) which animals had been taught to avoid. The results suggest that CGRP in the gustatory insular cortex is concerned with rejection or avoidance behaviors to aversive taste stimuli.

Animals↗
PubMed1990

Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit.

Perfusates were taken from the superficial layers of the subnucleus caudalis of the trigeminal sensory nuclear complex (SpVc), the first relay station of dental pain, with a push-pull cannula system and were assayed for endogenous serotonin (5-HT) and catecholamines by high-pressure liquid chromatography with an electrochemical detection. Spontaneous release of 5-HT and epinephrine was observed, while that of norepinephrine was not. Tooth pulp stimulation (ST) tended to increase the level of 5-HT in the perfusates. Pretreatment with morphine at a dose of 10 mg/kg (i.v.) significantly enhanced the release of 5-HT. However, there was no significant difference in morphine effect on the 5-HT level between stimulated and non-stimulated animals. Systemic administration of morphine (10 mg/kg i.v.) completely inhibited the release of immunoreactive substance P from the superficial layers of SpVc evoked by ST, and this inhibition was antagonized by local application of methysergide (10(-4) M). These results suggest that in the superficial layers of SpVc, morphine may primarily activate the descending 5-HT pathway which serves to modulate dental pain transmission.

Animals↗
PubMed1990

Release of calcitonin gene-related peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.

In a rat phrenic nerve-hemidiaphragm preparation, calcitonin gene-related peptide (CGRP) increased the twitch contraction induced by nerve or transmural stimulation dose dependently. Either electrical or high K+ stimulation of the phrenic nerve caused release of a CGRP-like immunoreactive substance (CGRP-LIS) in a Ca2(+)-dependent manner. Electrical stimulation of the phrenic nerve also increased the cyclic AMP content in diaphragm. This increase was not observed in Ca2(+)-free medium and was blocked by antiserum against CGRP. These results indicate that excitation of the motor nerve causes release of CGRP-LIS at nerve terminals and that the released CGRP-LIS increases the cyclic AMP content of skeletal muscles and potentiates twitch contraction.

Animals↗
PubMed1990

[Effects of 7 drugs on cutaneous blood flow evoked by electric stimulation of rat sciatic nerve].

The non-invasive technique of laser-Doppler flowmeter (LDF) was used to measure the change of cutaneous blood flow evoked by electric stimulation of rat sciatic nerve. The sciatic nerve was cut centrally and placed on bipolar electrodes. Drug were infused in a carotid artery. Electric stimulation of the sciatic nerve containing sensory afferent fibers caused an increase in cutaneous blood flow. This increase was not modified by the ia infusion of adrenergic blocking agents (phentolamine, 0.1 mg/kg and propranolol, 0.5 mg/kg), anti-muscarinic agent (atropine 0.5 mg/kg), anti-histamines (mepyramine, 10 mg/kg and cimetidine, 10 mg/kg) and 5-HT antagonist (methysergide, 0.5 mg/kg). Pretreatment with capsaicin (50 mg/kg, sc) in the newborn rat or the ia infusion of spantide (1, 2 mumol/kg) significantly inhibited the the stimulation-induced increase of the blood flow. These results suggest that substance P released from the peripheral endings of sensory nerve may be involved in vasodilation following electric stimulation of the sciatic nerve in rat.

Analgesics↗
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↗
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↗
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↗