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)

Tissue levels of substance P (SP) were determined by radioimmunoassay in cat dental pulps after unilateral electrical stimulation of the inferior alveolar nerve. Nerve stimulation (10 V, 10 Hz, 5 ms for 3 min) reduced the SP level at the stimulated side by approximately 40%, indicating a release of SP. Stimulation performed after infusion of morphine (0.3 mg/kg/min, i.v.) for 10 min did not reduce the pulpal SP-level. Naloxone (3 mg/kg, i.v.) administered immediately before the morphine infusion in three experiments, did not influence the effect of morphine on pulpal SP levels after nerve stimulation. This may indicate an action of morphine on a naloxone-insensitive receptor type. Morphine in the dosage used did not influence the intradental sensory nerve conductivity. The results indicate that morphine is able to inhibit stimulus evoked release of SP from peripheral endings of primary afferent neurons.
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PMID:Morphine inhibits substance P release from peripheral sensory nerve endings. 619 85

The pharmacology of the early and delayed phases of the neurogenic oedema responses to electrical stimulation of the saphenous nerve was studied in anesthetized rats using a quantitative Evans blue dye leakage technique. The immediate response to 5 min nerve stimulation was not reduced by aprotinin or mepyramine in combination with methysergide. However the response measured 10 min later and also that to 15 min nerve stimulation were reduced by these agents indicating that kinins and mast cell amines might be released after some delay, but they did not contribute significantly to the early phase of the response. Results with indomethacin indicated that prostaglandins were not involved in the later phase of the response. Bacitracin which has been reported to potentiate the sialogogic effect of substance P, the most likely candidate for primary mediator of neurogenic oedema, was without effect on the early phase of the response. Morphine, which has been suggested to inhibit stimulus-evoked substance P release from primary afferent terminals, reduced the early phase of the neurogenic oedema response but it also reduced blood pressure. Both effects were abolished by naloxone and thus it is likely that the reduction in the neurogenic oedema response was due to the depressor action of morphine. In confirmation of previous findings, capsaicin pretreatment of both adult rats and rats as neonates resulted in marked reduction of the neurogenic oedema response without effect on the vascular permeability response to substance P.
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PMID:Pharmacology of the neurogenic oedema response to electrical stimulation of the saphenous nerve in the rat. 723 72

We have previously reported that morphine produces a concentration-dependent multiphasic modulation (inhibitions and facilitations) of substance P (SP) release from trigeminal nucleus caudalis slices by activation of distinct populations of mu-, delta- and kappa-opioid receptors. In the present study, we have examined a wide range of morphine concentrations on K(+)-evoked SP release from dissociated rat dorsal root ganglion (DRG) neurons in culture. SP immunoreactivity was measured in the release buffer. Morphine produced a biphasic effect on K(+)-evoked SP release without affecting basal release. A concentration of 30 nM morphine facilitated SP release while a concentration of 1 microM suppressed release. Higher concentrations of morphine (10-30 microM) did not alter SP release. The facilitatory effect evoked by 30 nM morphine was abolished by opioid-receptor blockade with naloxone (30 nM) and the inhibitory effect produced by 1 microM morphine tended to be reversed. We conclude that an intact neuronal circuitry is not required for morphine to produce an opioid receptor mediated biphasic modulation of SP released from unmyelinated primary afferents. It is plausible that the dose-dependent biphasic effects of opioid agonists may also produce biphasic effects on nociception.
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PMID:Morphine produces a biphasic modulation of substance P release from cultured dorsal root ganglion neurons. 747 8

The effect of endogenous opioid receptor stimulation on the central cardiovascular and behavioral actions of substance P (SP) was examined in conscious rats. SP (55 pmol) injected intracerebroventricularly (i.c.v.) elicited increases in mean arterial pressure, heart rate, and stereotyped behavioral activation such as exploring and grooming, which were considered to be parts of the cardiovascular defense reaction. Intravenous (i.v.) pretreatment with morphine (2.5 and 5.0 mg/kg) attenuated the cardiovascular and behavioral responses produced by SP i.c.v. dose-dependently. The i.v. pretreatment with naloxone (10 mg/kg) had no effect on the central SP-induced response. Pressor responses elicited by i.c.v. injection of corticotropin-releasing factor or angiotensin II were also attenuated by pretreatment with i.v. morphine (5.0 mg/kg). Our results showed that endogenous opioid receptor stimulation antagonizes the central cardiovascular and behavioral actions of SP. Morphine may not influence the primary site of action of SP but does influence the central neural pathway which conveys the SP-induced sympathetic activation signal.
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PMID:Inhibition by morphine of the cardiovascular and behavioral responses evoked by centrally administered substance P in conscious rats. 751 72

The peptide NK1-receptor antagonists, sendide and [D-Trp7]sendide, have been evaluated for antinociceptive activity in the capsaicin test. Both peptides, injected intrathecally (i.t.) 5 min prior to intraplantar capsaicin, produced a dose-dependent reduction of the capsaicin-induced paw licking response. Naloxone (4.0 mg/kg) pretreatment did not affect sendide- and [D-Trp7]sendide-induced antinociception, whereas naloxone at a dose of 0.5 mg/kg antagonized the antinociceptive effect of i.t. administered morphine. Conversely, the antinociceptive action induced by both NK1-receptor antagonists was reduced significantly by i.t. co-administration of substance P. Morphine-induced antinociception was not antagonized by co-administration of substance P. These results led us to the understanding of differential action mechanism of NK1-receptor antagonist- and morphine-induced antinociception as assayed by the capsaicin test.
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PMID:Differential antinociceptive effects of sendide, a NK1-receptor antagonist, and morphine in the capsaicin test. 752 10

Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal cord. This question was investigated by use of the recently developed galanin receptor antagonists galantide [M-15, galanin-(1-13)-substance P-(5-11) amide] and M-35 [galanin-(1-13)-bradykinin-(2-9) amide]. Nociception was assessed in the rat tail-flick test using radiant heat and the rat Randall-Selitto model of inflammatory pain using vocalization as the nociceptive criterion. Intrathecal (i.t.) injections were performed in rats under either anaesthesia. Morphine was administered either i.t. or intraperitoneally (i.p.), and the antagonists were injected i.t. [125I]Galanin binding experiments were performed on crude synaptosomal membranes of the rat spinal cord. In the rat tail-flick test, i.t. injection of 3 micrograms morphine evoked antinociception of about 75% of the maximal possible effect (% MPE). Co-injection of either 2 micrograms galantide or 2 micrograms M-35 with morphine almost completely abolished the antinociceptive effect of morphine. I.p. injection of 2.15 mg/kg morphine elicited about 80% MPE when given 10 min prior to i.t. saline injection. Injection of the antagonists instead of saline antagonised the antinociceptive effect of morphine partially thus showing the spinal proportion of the overall antinociceptive effect. In the rat Randall-Selitto test, 3 micrograms morphine, injected i.t., produced antinociception of almost 100% MPE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spinal antinociception by morphine in rats is antagonised by galanin receptor antagonists. 753 Dec 94

The actions of clonidine, 5-bromo-N-(4,5-dihydro-1H-imidazole-2-yl)-6-quinoxalinamine (UK 14304), D-Ala2, N-MePhe4, Gly-ol5 enkephalin (DAGOL), and morphine on neurogenic contractions were studied in guinea pig ileum longitudinal muscle myenteric plexus in vitro. Cholinergic contractions were evoked by 0.1 and 10 Hz transmural electrical stimuli; noncholinergic contractions (1 microM scopolamine present) were evoked only by trains of stimuli. Noncholinergic contractions were mediated largely by substance P (SP). DAGOL and morphine inhibited 0.1 Hz contractions; pD2 values were 8.0 and 6.0, respectively. DAGOL also inhibited 10-Hz cholinergic contractions (pD2 = 7.5). The actions of DAGOL were blocked by naloxone (Kb approximately 5 nM) indicative of an action at mu opioid receptors. DAGOL (1 microM) reduced by 50% noncholinergic responses evoked by 5 Hz but not 10- or 20-Hz stimulation. Morphine did not inhibit noncholinergic contractions. Clonidine and UK 14304 inhibited 0.1 Hz contractions with pD2 values of 8.1 and 7.4, respectively. Clonidine and UK 14304 also inhibited 10-Hz cholinergic contractions. UK 14304 inhibited equally well noncholinergic contractions evoked by 5-, 10- and 20-Hz stimuli. The actions of UK 14304 were blocked by idazoxan (Kb approximately 5 nM). UK 14304 and DAGOL Ka values were determined using null methods and were used to construct occupancy-response curves to measure coupling efficiency (efficacy) between agonist-occupied receptor and response. The relative efficacy of UK 14304 was: 10 Hz noncholinergic > or = 0.1 Hz cholinergic > 10 Hz cholinergic. The relative efficacy for DAGOL was: 0.1 Hz cholinergic > 10 Hz cholinergic >>> 10 Hz noncholinergic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential inhibition of cholinergic and noncholinergic neurogenic contractions by mu opioid and alpha-2 adrenergic agonists in guinea pig ileum. 767 48

The effect of continuous intrathecal infusion with morphine (5 mu/h) or naloxone (2 micrograms/h) was investigated with regard to analgesia and the apparent density of mu- and delta-opioid and neurokinin-I/substance P receptors in the rat spinal cord. Morphine infusion increased tail-flick and paw-pressure responses until day 4 after the mini-osmotic pump implant. A decline in antinociception, reflecting tolerance to morphine, was then apparent in both tests. Quantitative in vitro receptor autoradiography of [125I]FK-33824, [125I][D.Ala2]deltorphin-I and [125I] Bolton-Hunter substance P binding sites, as ligands of mu, delta and neurokinin-I/substance P receptors, respectively, was performed on lumbosacral spinal cord sections of seven-days tolerant animals. Treatments with morphine and naloxone induced a similar increase (37%) in the number of delta binding sites in the superficial laminae of the dorsal horn. In contrast, the density of mu-opioid receptors was only affected by naloxone (50% increase). Neurokinin-I/substance P binding parameters were not altered by these treatments. Thus, it appears that delta-opioid binding sites may be of special relevance with regard to the development of tolerance to opiates in the spinal cord.
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PMID:Opioid and substance P receptor adaptations in the rat spinal cord following sub-chronic intrathecal treatment with morphine and naloxone. 768 33

Excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses have been shown to be mediated by the release of tachykinins from sensory nerves. We investigated whether bronchial-tube contractions evoked by electrical-field stimulation (EFS) or capsaicin coincided with the release of neurokinin A (NKA). We also studied the modulatory action of morphine and the ability of naloxone to affect these responses. We used a guinea pig bronchial-tube preparation denuded of epithelium. The method allows simultaneous measurement of smooth-muscle tension and mediator release. A significant release of NKA-LI, at 37.3% above the basal level, was detected in response to EFS. Morphine pretreatment was found to inhibit the release, and such inhibition was not prevented by naloxone. Contractile responses to EFS coincided with the NKA-LI release. Capsaicin stimulation evoked a significant release (35.4%) of NKA-LI, and this release was accompanied by contractions. Treatment with morphine decreased capsaicin-induced responses, and naloxone reversed the inhibitory effect. In conclusion, both capsaicin- and EFS-induced e-NANC responses were inhibited by morphine treatment. This indicates presynaptic inhibition of tachykinin release from sensory nerves. Furthermore, the ability of naloxone to reverse this inhibitory effect differed in capsaicin- and EFS-challenged preparations.
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PMID:Morphine modulates contractile responses and neurokinin A-LI release elicited by electrical field stimulation or capsaicin in a guinea pig bronchial-tube preparation. 769 49

Using the chronic constriction model (CCI) of Bennett and Xie (1988), changes in the lumbar spinal cord in neuropeptides and lectin IB4 were examined at 28 days post-nerve constriction and were compared with the degree of mechanical hyperalgesia. Animals following nerve ligation were significantly more hyperalgesic than sham-operated animals (P < 0.0001). Lectin IB4, a marker of primary afferent C fibres, showed a qualitative decrease in staining intensity in laminae 1-2 with ligation compared with both the unoperated contralateral side and with sham animals. Using fluorescent immunohistochemistry to quantify changes in neuropeptides in the dorsal horn we found that substance P showed significant decreases with ligation compared to sham operation (P < 0.002). CGRP and galanin showed no significant changes in laminae 1-2 compared to sham-operated animals. Neuropeptide Y (NPY) showed no significant changes in intensity in laminae 1-2; however, in laminae 3-4 there was a significant increase with nerve ligation compared to sham (P < 0.005). We examined how pre-emptive drug treatment affected these neuronal markers at 28 days. We used (1) clonidine, an alpha 2-adrenoreceptor agonist (1 mg/kg, i.p.), (2) morphine, a mu-opioid agonist (5 mg/kg, i.p.) or (3) MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist (0.3 mg/kg, s.c.) administered 30 min prior and 6 h following nerve ligation or sham-operation. Hyperalgesia in the ligated group at 28 days was suppressed by treatment with pre-emptive clonidine (P = 0.003) or MK-801 (P = 0.003) but not morphine. With the exception of NPY there was no effect of pre-emptive drug treatment on any neuronal marker examined. Pre-emptive MK-801 reduced the magnitude of the increase in NPY in laminae 3-4 in the ligated group (P < 0.005) and clonidine showed a similar trend but this did not reach significance. Morphine had no effect on NPY staining. There was a significant correlation between the increase in NPY staining in laminae 3-4 and the degree of hyperalgesia (r = 0.6, P < 0.001). These results suggest that the increased NPY expression in laminae 3-4 of the spinal cord (the territory of the myelinated sensory input) may be crucial to the development of hyperalgesia in this model.
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PMID:Changes in neuronal markers in a mononeuropathic rat model relationship between neuropeptide Y, pre-emptive drug treatment and long-term mechanical hyperalgesia. 857 86


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