Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to determine the effect of the opioid peptide dynorphin-(1-8) on the release of substance P-like immunoreactivity in the dorsal horn during mechanical activation of peripheral nociceptors. A push-pull cannula was used to perfuse the dorsal horn of decerebrate/spinal transected rats before, during and following the application of a noxious mechanical stimulus to the ipsilateral hindpaw and lower limb. The collected perfusates were assayed for substance P-like immunoreactivity using radioimmunoassay. Dynorphin-(1-8) applied to the spinal cord at a concentration of 1 microM reduced the basal release of substance P-like immunoreactivity by 28 +/- 11% and prevented the mechanically evoked release of substance P-like immunoreactivity. This effect of dynorphin-(1-8) was reversed by 2 microM of the selective kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, blockade of the kappa-opioid receptors by nor-binaltorphimine resulted in a 33 +/- 5% increase in the basal release of substance P-like immunoreactivity. These data show that activation of nor-binaltorphimine-sensitive sites by dynorphin-(1-8) results in inhibition of the release of substance P-like immunoreactivity in the dorsal horn of the rat.
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PMID:Dynorphin-(1-8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus. 912 34

Previous studies have shown that the striatum provides synaptic inputs to the globus pallidus and entopeduncular nucleus in which GABA is co-localized with the peptides enkephalin and substance P. The aim of this study in the rat was to determine whether the striatal projections also make synaptic contact with the cholinergic neurons of the nucleus basalis, which lie near to the pallidal areas in the rat brain. The anterograde tracer biocytin was injected into different parts of the striatum, and brain sections were stained for biocytin and choline acetyltransferase immunoreactivity by using a dual colour method. Terminals labelled with biocytin by anterograde transport and which made synaptic contact with choline acetyltransferase-positive soma and dendrites were identified by light-electron microscopic correlation methods. In the cases where the biocytin injections had been made in the dorsal or lateral striatum, biocytin-labelled terminals made synaptic contact with cholinergic cells in the region between the main termination zones in the globus pallidus and the entopeduncular nucleus. In the cases where the injections had been made in the ventromedial and posterior striatum, there was greater overlap between choline acetyltransferase-positive structures and biocytin-labelled terminals in the main termination zones in the globus pallidus or entopeduncular nucleus, but relatively few of these terminals made synaptic contacts on to the cholinergic neurons. The results therefore indicate that the cholinergic nucleus basalis cells receive a relatively sparse synaptic input from all parts of the striatum. It has recently been shown that the cholinergic cells of the nucleus basalis selectively express high levels of substance P and opioid receptor messenger RNAs, while the non-cholinergic pallidal cells have much higher levels of GABA(A) receptor subunit messenger RNAs. It is concluded that the cholinergic neurons of the nucleus basalis in the rat may be selectively responsive to the peptidergic components of the striatal outputs, and that they are most likely to be influenced by both the limbic and sensorimotor parts of the striatum.
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PMID:The projection from the striatum to the nucleus basalis in the rat: an electron microscopic study. 917 63

Coexistence of mu-opioid receptor (MOR)-like immunoreactivity (LI) and substance P (SP)-LI in the neurons of the cat dorsal root ganglia (DRG) was examined by a double immunofluorescence histochemical method. Approximately 91% of SP-LI neurons in the DRG showed MOR-LI. However, SP-LI was exhibited in approximately 28% of the neurons labeled with MOR-LI. These morphological findings indicated that the MOR exist on most of the primary afferent SP-containing terminals, and suggest that MOR may regulate SP release from the primary afferent terminals in the cat dorsal horn.
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PMID:Coexistence of mu-opioid receptor-like and substance P-like immunoreactivities in the cat dorsal root ganglionic neurons. 917 36

1. We set out to ascertain the role of tachykinins, neurokinin A and substance P, in castor oil-induced diarrhoea in rats as disclosed by the inhibitory effect of the non-peptide NK1- and NK2-receptor antagonists. SR 140333 and SR 48968, respectively. 2. SR 48968 (0.02 to 20 micrograms kg-1, s.c. or p.o.), and the opioid receptor agonist loperamide (1-10 mg kg-1, p.o.), dose-dependently prevented castor oil effects: % inhibition vs castor oil, diarrhoea 0 to 100, increase in faecal mass 7 to 90 and water content 16 to 90. SR 140333 (0.02 to 20 micrograms kg-1, s.c.) and the platelet activating factor antagonist SR 27417 (5 to 500 micrograms kg-1, p.o.) did not prevent the increase in faecal water content, but reduced faecal mass (35 to 66%) and diarrhoea (0 to 57%). 3. The R-enantiomers of tachykinin NK1 and NK2 receptor antagonists, SR 140603 and SR 48605 (both at 2 or 20 micrograms kg-1, s.c.) had no effect other than reducing faecal mass at the highest dose tested. 4. SR 48968 (20 micrograms kg-1, p.o.) but not loperamide (10 mg kg-1, p.o.) given 24 h before castor oil, still slightly but significantly reduced by 30% the increase of faecal mass output; both treatments significantly reduced (30 to 70%) the effect of castor oil on faecal water content, although the incidence of diarrhoea was only slightly less than in controls. 5. In castor oil-treated rats, naloxone (2 mg kg-1, s.c.) completely blocked the antidiarrhoeal action of loperamide (10 mg kg-1, p.o.) but not of SR 48968 (20 micrograms kg-1, p.o.): a similar result was obtained on faecal mass and water content. 6. Castor oil strongly increased the occurrence of manometrically recorded propulsive giant contractions (500 to 1000% over control values) of transverse and distal colon, this effect being significantly prevented (80 to 100%) by SR 48968 and loperamide and partially by SR 140333 (35% distal colon, 70% transverse colon). 7. In castor oil free rats, loperamide but not SR 48968 or SR 140333 significantly reduced by 50% the gastrointestinal transit of a charcoal test meal, as well as 24 h faecal mass output. Consistently, loperamide, unlike the tachykinin receptor antagonists, had a dramatic effect on manometric recordings of intestinal motility, reducing all kinds of colonic contractions. 8. Our findings suggest that castor oil diarrhoea in rats entails activation of NK1 and NK2 receptors by endogenous tachykinins, whose antagonists may have a potential as antidiarrhoeal agents free from the constipating action of opioids.
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PMID:Role of tachykinins in castor oil diarrhoea in rats. 917 76

The functional interaction between substance P (SP) and N-methyl-D-aspartate (NMDA) was studied to clarify the diversity of the roles of SP in nociceptive processes at the spinal level in mice. Behavioral responses elicited by intrathecal co-administration of NMDA (0.25 nmol) with various doses of SP (0.3-12 pmol) were observed for 1 min. The high dose of SP (12 pmol) potentiated NMDA-induced responses, which consisted of caudally directed licking and biting, while the low dose of SP (1 pmol) significantly reduced the responses by 40% compared to control mice administered NMDA alone. The antinociceptive effect of the low dose of SP was negated by co-administration of the opioid receptor antagonist naloxone. Furthermore, the antinociception produced by SP was present in mice pre-treated with systemic administration of capsaicin during the neonatal period. These results suggest that one of the roles SP plays at the spinal level is an involvement in antinociception. The activities of excitatory dorsal horn neurons are considered to be inhibited by endogenous opioid peptides released from inhibitory dorsal horn neurons directly stimulated by SP.
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PMID:Antinociceptive involvement of substance P in the spinal cord of mice: dose effects of substance P on the behavior elicited by intrathecally administered NMDA. 922 43

Intracerebral microdialysis was used to measure changes in the extracellular level of substance P (SP) released from the periaqueductal gray (PAG) and the preoptic anterior hypothalamus (POAH) of freely moving Sprague-Dawley rats after noxious cold stimulation. Artificial cerebrospinal fluid was perfused into the dialysis probe in the PAG or POAH and samples were collected every 30 min for 4 hr. SP-like immunoreactivity in the samples was measured by radioimmunoassay. In the PAG, SP base-line release was 0.43 +/- 0.08 fmol/fraction. SP release was increased to 1.3 +/- 0.4 fmol/fraction during the first collection period after noxious cold. Pretreatment with the selective mu opioid receptor agonist PL017 (0.8-3.4 nmol) or the kappa opioid receptor agonist dynorphin A1-17 (4.6-9.2 nmol), administered into the PAG by microinjection, produced dose-related inhibition of the cold-evoked SP release. Naloxone (10 mg/kg s.c.) administration 10 min before these opioid agonists reduced the inhibition of SP release. In the POAH, SP base-line release was 0.45 +/- 0.06 fmol/fraction and noxious cold did not cause any significant change in SP release. Microdialysis of SP (271 fmol-271 pmol/microl/min, for 30 min) into the PAG, but not the POAH, induced dose-related analgesia (35-68% MPA) in the cold-water tail-flick test. However, microdialysis of SP into the POAH or PAG failed to induce any significant change in body temperature. These data suggest that 1) SP released from the PAG acts as a neuromodulator to transmit nociceptive information; 2) opioid receptor agonists can suppress this information by inhibiting SP release; 3) SP evoked by noxious cold may have a role in triggering the antinociceptive function of the PAG; and 4) SP does not appear to act as a neuromodulator for thermoregulatory responses in the POAH.
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PMID:Substance P release in the rat periaqueductal gray and preoptic anterior hypothalamus after noxious cold stimulation: effect of selective mu and kappa opioid agonists. 926 75

Two highly-selective mu-opioid receptor agonists, endomorphin-1 and -2, were recently purified from bovine brain and are postulated to be endogenous mu-opioid receptor ligands. We sought to determine the effects of these ligands at the spinal level in mice. Endomorphin-1 and -2 produced short acting, naloxone-sensitive antinociception in the tail flick test and inhibited the behavior elicited by intrathecally injected substance P. Both endomorphin-1 and -2 were anti-allodynic in the dynorphin-induced allodynia model. Although acute tolerance against both endomorphins developed rapidly, endomorphin-1 required a longer pretreatment time before tolerance was observed. We conclude that the endomorphins are potent spinal antinociceptive and anti-allodynic agents and that they or related compounds may prove therapeutically useful as spinal analgesics.
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PMID:Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2. 933 28

Using immunohistochemistry and immunoelectron microscopy, the localization and regulation of delta-opioid receptor-like immunoreactivity were studied in dorsal root ganglia and spinal cord of normal rat and monkey, and after peripheral axotomy. Delta-opioid receptor-like immunoreactivity was observed in many small dorsal root ganglion neurons, and in the rat most of them contained substance P and calcitonin gene-related peptide. At the ultrastructural level, delta-opioid receptor-like immunoreactivity was localized in the Golgi complex, on the membrane of the large dense-core vesicles and on the membrane of and/or inside a type of large vesicle with an interior of low electron density. The latter vesicles were often in contact with multivesicular bodies. In the superficial dorsal horn of the spinal cord, most delta-opioid receptor-positive nerve fibers contain substance P and/or calcitonin gene-related peptide, both in rat and monkey. Also, in these nerve endings delta-opioid receptor-like immunoreactivity was found on the membrane of large dense-core vesicles and on the membrane of, or in, the lucent vesicles. Occasionally, delta-opioid receptor-like immunoreactivity was observed on the plasmalemma of the terminals, particularly when the vesicles were in exocytotic contact with the plasmalemma. Peripheral axotomy induced a decrease in delta-opioid receptor-like immunoreactivity both in cell bodies in the dorsal root ganglia and in terminals in the dorsal horn. These data suggest that the delta-opioid receptor may be a constituent of the membrane of large dense-core vesicles storing and releasing neuropeptides. It is suggested that upon exocytotic release of substance P and calcitonin gene-related peptide from large dense-core vesicles, there is a transient modification of the surface of the primary afferent terminals which leads to exposure of the receptor protein so that enkephalin released from adjacent terminals can activate the receptor. The decrease in delta-opioid receptors after axotomy indicates that delta-opioid receptor-mediated inhibitory effects are attenuated at the spinal level both in the rat and monkey.
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PMID:Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles. 946 42

We tested the effects of (3 R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-1-indancarbony l]-2,3,5,6-tetrahydro-1,4-thiazine hydrochloride (R-84760), a selective kappa-opioid receptor agonist, on the slow ventral root potential in the isolated spinal cord of neonatal rats. R-84760 at 10 nM decreased the slow ventral root potential to 35% of the control, leaving the monosynaptic reflex unaffected. The depressant effect of R-84760 progressed slowly for 60 min to the maximum and recovered slightly after removal of the drug from the perfusing solution. This contrasts with [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) or [MeTyr1, MeArg7, D-Leu-NHEt8]dynorphin A-(1-8) (E-2078) which attained their maximum depressant effect within 15 min with recovery immediately after washout. Reversibility of the R-84760 effect was observed in vivo in antinociceptive tests in mice. R-84760 reduced the depolarization induced by substance P or L-glutamate in the normal solution, but not in the presence of tetrodotoxin at 0.3 microM. Naloxone inhibited the effect of R-84760 at a higher concentration (1 microM) than that (0.1 microM) needed to antagonize the effect of DAMGO. In contrast, R-84760 was more sensitive to nor-binaltorphimine than was DAMGO. The results show that R-84760 selectively inhibits the nociceptive response presynaptically through kappa-opioid receptors and that the inhibitory effect is characteristic, with long duration, in the neonatal rat spinal cord.
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PMID:Effects of R-84760, a selective kappa-opioid receptor agonist, on nociceptive reflex in isolated neonatal rat spinal cord. 957 Apr 65

Nociceptin is a novel neuropeptide of the opioid peptide family recently identified as the endogenous ligand of the opioid receptor-like "orphan" receptor. Unlike other opioids, nociceptin has hyperalgesic effects in vivo. In the present study, nociceptin was found to inhibit electrical field stimulation-induced tachykinergic contractions of the guinea pig isolated bronchus preparation. The threshold effect was about 1 nM, and at 0.1 microM, nociceptin inhibited contractions evoked by 5-Hz stimulation by more than 50%. This inhibitory effect was found to be mediated by a prejunctional mechanism involving none of the classical (mu, delta and kappa) opioid receptors. Although the hypothesis that the effect of nociceptin was secondary to opioid receptor-like stimulation cannot be pharmacologically addressed, opioid receptor-like-receptor-mRNA was found to be expressed in the upper vagal sensory ganglion, where the cell bodies of the tachykinin-containing sensory neurons are located. Nociceptin immunoreactive nerve fibers in the airway wall, distinct from the tachykinin-containing fibers, were identified as an endogenous source of nociceptin. These data indicate that nociceptin may influence airway physiology by modulating tachykinergic neurotransmission.
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PMID:Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus. 958 Jun 42


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