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)

In the rabbit iris sphincter muscle, transmural electrical stimulation produces cholinergic and substance P-ergic responses. In the present work, the effects of dynorphin-(1-13), an endogenous ligand of the kappa opioid receptor, on these two neurogenic responses were examined pharmacologically and the data compared to findings in case of other opioid agonists. Dynorphin-(1-13) (10(-7) to 10(-6) M) enhanced the cholinergic responses and attenuated the substance P-ergic response, in a concentration-dependent manner, and these actions of dynorphin-(1-13) were more apparent in the case of low-frequency stimulation. These effects of dynorphin-(1-13) were antagonized by naloxone (10(-5) M). Dynorphin-(1-13) had no effects on the responses to exogenously applied acetylcholine, carbachol and substance P. The augmenting effect on the cholinergic transmission was unique in kappa agonists, as the cholinergic responses were also augmented by other kappa agonists such as dynorphin-(1-17) and ethylketocyclazocine, but attenuated by other opioid agonists (Met-enkephalin, beta-endorphin and morphine) and not affected by SKF-10,047 and nalorphine. On the other hand, the substance P-ergic response was attenuated by all the opioids used. These results suggest that dynorphin-(1-13) presynaptically increases the release of acetylcholine from the parasympathetic postganglionic nerves and reduces the release of substance P from the trigeminal nerve, mediated by kappa type of opioid receptors.
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PMID:Dual effects of dynorphin-(1-13) on cholinergic and substance P-ergic transmissions in the rabbit iris sphincter muscle. 257 68

The modulation of the release of substance P (SP) from sensory primary afferents by activation of kappa opioid receptors is not only equivocal, but also contradictory. Thus, in the present study, we have determined the effect of nanomolar concentrations of the highly selective kappa opioid receptor agonist trans-(+)-3,4-dichloro-N-methyl-N-[2-91- (pyrrolidinyl)cyclohexyl]benzacetamide methane sulphonate (U50488H), as well as micromolar concentrations of moderately mu-selective agonist morphine, on K(+)-evoked SP release from rat trigeminal nucleus caudalis slices. U50488H (10-30 nM) and morphine (10-30 microM) increased K(+)-evoked SP release without stimulating basal SP release. Both U50488H and morphine concentration-response curves were biphasic because the highest and the lowest concentrations of U50488H (100 nM) and morphine (3 microM) tested, respectively, inhibited SP release. Enhancement of K(+)-evoked SP release induced by 30 nM U50488H and 30 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; nontype selective) and norbinaltorphimine (3 nM; kappa selective), but not by N,N diallyl Tyr-Aib-Aib-Phe-Leu (0.3 microM; delta selective), naloxonazine (1 nM; mu 1 selective) or beta-funaltrexamine (20 nM; mu selective). These findings indicate that activation of at least one population of kappa opioid receptors increases the release of SP from trigeminal nucleus caudalis. Excitatory presynaptic kappa opioid receptors on SP-containing primary afferents may be involved in the hyperalgesia of inflammatory processes, the "anti-analgesic" effect of dynorphin and the paradoxical "analgesia" produced by low doses of naloxone.
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PMID:Activation of kappa opioid receptors by U50488H and morphine enhances the release of substance P from rat trigeminal nucleus slices. 767 33

Since opioids can influence the release of acetylcholine, substance P and a number of other neurotransmitters that have been implicated in the pathogenesis of Alzheimer's disease (AD), it is of interest to assess opioid receptor levels in AD. We have examined mu, delta and kappa opioid receptor binding parameters, binding sensitivity to a GTP analog and distribution in amygdala, frontal cortex and putamen of AD brain. Control brains were matched according to age, sex, post-mortem interval and storage time. Kd values and GTP analog binding sensitivity did not differ in AD and control brains. Bmax values for mu ([3H]DAMGE) sites also appeared unaffected by in vitro binding assays. In contrast, kappa ([3H]U69593) and delta ([3H]DSLET) opioid receptor levels, were significantly changed. In AD amygdala kappa Bmax values increased from control levels of 123 +/- 12 to 168 +/- 13 fmol/mg protein, whereas densities of kappa and delta sites were decreased from 94 +/- 8 to 48 +/- 8 and 102 +/- 3.6 to 69 +/- 8.5 fmol/mg protein, respectively, in putamen. Autoradiography revealed corresponding differences in the distribution of kappa opioid receptors. The findings indicate that the kappa binding site, which is quantitatively the major opioid receptor class in human brain, undergoes marked changes in AD amygdala and putamen.
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PMID:Opioid receptor density changes in Alzheimer amygdala and putamen. 814 29

Substance P (SP), a member of the tachykinin peptide family, has been found in high concentrations in the superficial laminae of the dorsal horn and it is thought to play a major role in the transmission of nociceptive information. Dynorphin(1-8), an opioid peptide with high selectivity for the kappa-opioid receptor subtype, is also found in the dorsal horn of the spinal cord. The aim of this study was to determine the effect of dynorphin(1-8) on the release of SP-like-immunoreactivity (SPLI) in the dorsal horn before and during the activation of peripheral nociceptors by a thermal stimulus. A push-pull canula was used to perfuse the dorsal horn of non-anesthetized decerebrate/spinal transected rats and the collected perfusates were assayed for SPLI by using radioimmunoassay. Dynorphin(1-8) applied to the spinal cord at a concentration of 1 microM elicited a 27 +/- 8% decrease in the basal release of SPLI and prevented the increase in the release of SPLI evoked by the application of a noxious thermal stimulus to the ipsilateral hind paw and lower limb. The effect of dynorphin(1-8) was reversed by 2 microM of nor-binaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist. Application of nor-BNI alone to the perfusate resulted in a 62 +/- 23% increase in the basal release of SPLI. In conclusion, dynorphin(1-8) reduces the basal release of SPLI and prevents the increase in the release of SPLI elicited by the application of a noxious cutaneous thermal stimulus. This effect is mediated through the kappa-opioid receptor, which appears to tonically regulate the release of SPLI in the dorsal horn.
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PMID:Kappa-opioid receptor modulation of the release of substance P in the dorsal horn. 872 Apr 94

The novel heptadecapeptide opioid, nociceptin, produced a concentration-dependent (EC50 28 nM) suppression of the inotropic response of the guinea-pig isolated renal pelvis to electrical stimulation, a response mediated by release of tachykinins from sensory nerves. Nociceptin did not affect the response to neurokinin A, indicating a prejunctional site of action on tachykininergic nerves. The effect of nociceptin was unchanged in the presence of the mu, delta and kappa opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine.
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PMID:Inhibition of tachykinin release from peripheral endings of sensory nerves by nociceptin, a novel opioid peptide. 884 16

In 1992, Xie et al. identified a cDNA sequence in the expression cloning search for the kappa opioid receptor. When the cDNA was expressed in Cos-7 cells, binding of opioid compounds was observed to be of low affinity and without kappa, mu, or delta selectivity [Xie, G.-X., Miyajima, A. and Goldstein, A. (1992) Proc. Natl. Acad. Sci. USA 89, 4124-4128]. This cDNA was highly homologous to the human neurokinin-3 (NK-3) receptor sequence, and displayed lower homology to NK-1 and NK-2 sequences. This sequence was stably expressed in Chinese hamster ovary cells, which do not express neurokinin receptors naturally, and ligand binding and second messenger characteristics were compared with a human NK-3 receptor. The NK-3 receptor homolog bound [3H] senktide with a Kd of 39 nM, similar to that of the NK-3 receptor. The rank order of tachykinin peptides competing for [3H]senktide binding at the NK-3 receptor homolog was [MePhe7]neurokinin B > senktide > substance P = neurokinin A > neurokinin B. This cell line also bound [125I-MePhe7]neurokinin B; however, neurokinin B was an effective competitor. Tachykinin peptides stimulated both inositol phospholipid hydrolysis and arachidonic acid release at NK-3 and NK-3 receptor homolog cell lines, with similar rank orders of potency of [MePhe7] neurokinin B = neurokinin B = senktide > NKA = substance P. These results indicate that expression of the NK-3 receptor homolog cDNA in the Chinese hamster ovary cell system induces the expression of a receptor site with many similarities but certain key differences from that of the human NK-3 receptor. The results are discussed with reference to the existence of a novel human tachykinin receptor.
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PMID:Functional expression of a novel human neurokinin-3 receptor homolog that binds [3H]senktide and [125I-MePhe7]neurokinin B, and is responsive to tachykinin peptide agonists. 899 Feb 5

We have previously shown that kappa opioid receptor-like immunoreactivity (KT-LI) is present in axons and terminals in the granule cell layer and inner molecular layer of the guinea pig dentate gyrus. The distribution and ultrastructural appearance of processes with KT-LI were similar to those of the substance P (SP)-containing afferents which arise from the supramammillary region of the hypothalamus (SUM) and enter the hippocampal formation through the fimbria-fornix. The objective of the present study was to determine whether the terminals with KT-LI are likely to be SUM afferents. To accomplish this we 1) compared the intensity of KT- and SP-immunolabeling in the dentate gyrus ipsilateral and contralateral to a unilateral fornix transection and 2) used dual-labeling electron microscopy to determine whether terminals with KT-LI colocalize SP-LI in the dentate gyrus. Light microscopic examination of the dentate gyrus demonstrated that KT-LI and SP-LI were in thin processes with overlapping distributions in strata granulosum and moleculare. Following fornix transection, both KT-LI and SP-LI were dramatically reduced in these regions of the dentate gyrus ipsilateral to the transection, consistent with an SUM origin. By electron microscopy, most (71%) terminals with KT-LI also contained detectable SP-LI in single-section analysis. Many dual-labeled terminals formed thick asymmetric synaptic contacts with large dendritic shafts (2-5 microns) or granule cell perikarya, and a smaller proportion contacted dendritic spines; these characteristics resembled those of identified SUM afferents in other species. The demonstrations that 1) KT-LI colocalizes with SP-LI in a morphologically distinctive population of axon terminals and 2) most of the processes with KT-LI enter through the fimbria-fornix suggest that kappa opioid receptors are present in the SUM projection to the dentate gyrus.
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PMID:Kappa opioid receptor-like immunoreactivity is present in substance P-containing subcortical afferents in guinea pig dentate gyrus. 913 67

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

The influence of chronic morphine and spontaneous withdrawal on the expression of dopamine receptors and neuropeptide genes in the rat striatum was investigated. Morphine dependence was induced by subcutaneous implantation of two morphine pellets for 6 days. Rats were made abstinent by removal of the pellets 1, 2 or 3 days before they were killed. The mRNA levels coding for D1- and D2-dopamine receptors, dynorphin, preproenkephalin A and substance P were determined by quantitative in situ hybridization. The caudate putamen and the nucleus accumbens showed equivalent modifications in dopamine receptor and neuropeptide gene expression. After 6 days of morphine, a decrease in D2-dopamine receptor and neuropeptide mRNA levels was observed (-30%), but there was no change in D1-dopamine receptor mRNA. In abstinent rats, both D1- and D2-dopamine receptor mRNA levels were decreased 1 day after withdrawal (-30% compared with chronic morphine). In contrast, neuropeptide mRNA levels were unaffected when compared with those observed after 6 days of morphine. During the second and third day of withdrawal, there was a gradual return to the levels seen in the placebo-treated group, for both dopamine receptor and neuropeptide mRNAs. Phenotypical characterization of striatal neurons expressing mu and kappa opioid receptor mRNAs showed that, in striatonigral neurons, both mRNAs were colocalized with D1-receptor and Dyn mRNAs. Our results suggest that during morphine dependence, dopamine and morphine exert opposite effects on striatonigral neurons, and that effects occurring on striatopallidal neurons are under dopaminergic control. We also show that withdrawal is associated with a down regulation of the postsynaptic D1 and D2 receptors.
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PMID:Chronic morphine exposure and spontaneous withdrawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum. 1005 49

The purpose of this study was to investigate the role that kappa opioid receptor stimulation has upon stimulant-induced behavior and neuropeptide gene expression in the striatum. Acute administration of amphetamine (2.5 mg/kg i.p.) caused an increase in behavioral activity and preprodynorphin, substance P, and preproenkephalin mRNA expression. When amphetamine-treated rats were pretreated with U69593, a kappa agonist (0.16 or 0.32 mg/kg s.c.), there was a significant decrease in behavioral activity. Quantitative in situ hybridization histochemistry revealed that 0.32 mg/kg U69593 significantly decreased amphetamine-induced mRNA expression of all three neuropeptides; however, only the induction of preproenkephalin mRNA was decreased by 0.16 mg/kg. These data suggest that stimulation of kappa receptors decreases acute amphetamine-induced behavior and mRNA expression of neuropeptides in the rat striatum.
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PMID:Kappa opioid receptor stimulation decreases amphetamine-induced behavior and neuropeptide mRNA expression in the striatum. 1153 35


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