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)

Capsaicin treatment (50 mg/kg, subcutaneous) of newborn rats resulted in 1 75% decrease of substance P immunoreactivity in the dorsal spinal cord of the adult animal, but failed to affect levels of the proposed sensory neurotransmitter glutamic acid or to alter high-affinity uptake of [3H]glutamic acid into synaptosomes of the same tissue. Furthermore, capsaicin (30 microM) in vitro had no influence on the release of [3H]glutamic acid from spinal cord P2 fractions of untreated adult rats, but induced a marked release of substance P. The results suggest that, in contrast to substance P fibers, neurons containing glutamic acid are not sensitive to capsaicin. Eleven other neurochemical parameters measured in the spinal cord did not appear to be changed by the treatment with capsaicin, suggesting a considerable neurochemical selectivity of the lesion.
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PMID:Capsaicin does not change tissue levels of glutamic acid, its uptake, or release in the rat spinal cord. 617 98

L-Glutamic acid or substance P were applied to the caudate nucleus (CN) or substantia nigra (SN) and their effects on local, spontaneous, in vivo [3H]serotonin ([3H]5-HT) release as well as [3H]5-HT release in the contralateral CN and SN were studied using cats implanted with push-pull cannulae. L-Glutamic acid (5 x 10(-5) M), when applied to the CN or SN inhibited the local release of [3H]5-HT but did not affect release in the contralateral CN and SN. In the SN, the L-glutamic acid effect was blocked by L-glutamic acid diethylester. Substance P (10(-7) M) applied to the SN induced an increase in [3H]5-HT release that was delayed in onset. Furthermore, [3H]5-HT release was elevated in the contralateral CN immediately upon the application of substance P to the SN. These results suggest that L-glutamic acid and substance P may control 5-HT transmission in the basal ganglia.
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PMID:Application of L-glutamic acid and substance P to the substantia nigra modulates in vivo [3H]serotonin release in the basal ganglia of the cat. 617 81

The conformation of several naturally occurring peptide hormones and bioactive oligopeptides in phospholipid solutions was studied by circular dichroism. Phosphatidylcholine induced a partial helix in human gastrin I at neutral pH, but phosphatidylserine did not unless the five consecutive glutamic acid residues in gastrin were protonated. Reduced somatostatin with two lysines and substance P with one arginine and one lysine were partially helical in phosphatidylserine, but not phosphatidylcholine, solution. Both lipids induced a helical conformation in glucagon and its COOH-terminal fragment (19-29) probably because the helical segment is primarily located at the uncharged COOH terminus. Thus, polypeptides with a helix-forming potential can have the helical conformation only when the peptides carry no charge or charges opposite to those on the polar head of the lipid. Renin substrate, which has potentials for the beta form and beta turn, seemed to form a mixture of the two conformations in phosphatidylserine solution. Angiotensin I with a strong probability for the beta form adopted the beta form in phosphatidylserine solution and sleep peptide with no structure-forming potential remained unordered in lipid solutions. The helix usually predominated over the beta form in lipid solutions if the peptide has potentials for both conformations. This could account for the preponderance of helices in bacteriorhodopsin of the purple membrane, which according to its amino acid sequence would have favored the beta form.
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PMID:Lipid-induced ordered conformation of some peptide hormones and bioactive oligopeptides: predominance of helix over beta form. 618 2

In the isolated spinal cord of the newborn rat, methysergide and LSD-25 depressed the monosynaptic reflex discharge selectively. Cyproheptadine and dimethothiazine did not inhibit the monosynaptic reflex. The selective inhibitory effect of methysergide on the monosynaptic reflex was not due to a presumptive low safety factor of this reflex. The inhibition was restored under a condition such as the compound action potential in the dorsal root was enhanced by 4-aminopyridine. Methysergide did not decrease the sensitivity of the motoneuron to substance P and L-glutamic acid. It is suggested that methysergide acts at the presynaptic terminal of Ia afferent fibers and depresses evoked transmitter release.
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PMID:Selective inhibition by methysergide of the monosynaptic reflex discharge in the isolated spinal cord of the newborn rat. 717 97

The neurokinin-1 tachykinin receptor is a member of the G protein-coupled receptor superfamily. An unusual feature of the neurokinin-1 receptor is the presence of glutamic acid (residue 78) in the second putative transmembrane domain, at the location of a highly conserved aspartate residue in the G protein-coupled receptor superfamily. The rat neurokinin-1 receptor cDNA was mutated to lysine, aspartate, and glutamine at this site and functionally expressed in Chinese hamster ovary cells, and clonal cell lines were isolated and characterized. Radioligand binding demonstrated that the Asp78 and Lys78 receptors have substance P binding affinities indistinguishable from those of the wild-type receptor and are expressed at roughly the same number of receptors per cell. The Gln78 receptor variant, on the other hand, exhibited no detectable agonist binding. Although wild-type and Asp78 receptors have essentially the same ability to stimulate inositol phospholipid turnover, cAMP production, and arachidonic acid release, the Lys78 variant is markedly attenuated in its ability to activate any of these pathways. These data indicate that residue 78 plays a role in the coupling of the rat neurokinin-1 receptor to cellular effectors. In addition, both Asp78 and Lys78 receptors show a greater percentage of high affinity binding that is resistant to guanosine-5'-O-(3-thio)triphosphate than does the wild-type receptor, indicating a potential difference in G protein coupling between wild-type and mutated receptors.
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PMID:Residue 78 in the second transmembrane domain of the neurokinin-1 receptor is important in coupling high affinity agonist binding to multiple second messenger responses. 753 94

In order to shed some light on the neurotransmitters in the spinothalamic tract (STT), we examined, biochemically and immunohistochemically, the contents of various neurotransmitter candidates in the terminal field of the STT after cervical hemi-chordotomy (HC) and dorsal quadrant-chordotomy (dQC) in the rat. Substance P (SP), calcitonin gene-related peptide (CGRP), enkephalin, neuropeptide Y, neurotensin, oxytocin and dynorphin A were analyzed immunohistochemically. The contents of neuropeptides (SP, CGRP and cholecystokinin octapeptide) were measured by radioimmunoassay and those of amino acids (aspartic acid, glutamic acid, gamma-aminobutyric acid (GABA) and glycine) and noradrenaline were determined using high-performance liquid chromatography. Cervical hemi-chordotomy, but not dQC, caused significant decreases of the SP-like immunoreactivity in and SP content of the ventral thalamus on the ipsilateral side, compared with that on the contralateral side and of rats subjected to sham-operation. However, neither HC nor dQC resulted in any changes in the ventral thalamic contents of other putative neurotransmitters examined. These results suggest that, in rats, the STT contains SP and that SP-positive fibers run in the ventral half of the ascending spinal tract at the cervical level.
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PMID:Substance P is a possible neurotransmitter in the rat spinothalamic tract. 753 53

In order to determine whether nitric oxide (NO) acts directly upon nerve terminals to regulate the synaptic transmission at the level of spinal cord, effects of NO-donors on release of substance P (SP) and glutamic acid (Glu) were investigated by superfusion of synaptosomes prepared from the rat spinal cord. Basal levels of endogenous SP and Glu release were 5.99 +/- 2.50 fmol/min/mg of protein and 26.2 +/- 4.8 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCI evoked 2.7- and 3.8-fold increases in SP and Glu release in a calcium-dependent manner, respectively. Sodium nitroprusside (NP) caused a reduction in the depolarization-evoked overflow of SP in a concentration-dependent manner without affecting its basal release, although it failed to affect either basal or evoked release of Glu. The reduction in SP overflow was also observed by the perfusion with S-nitroso-N-acetyl-penicillamine or membrane-permeable cyclic GMP, but not with cyclic AMP. NP caused the concentration-dependent increases in cyclic GMP levels in synaptosomes. Together with reports that excitatory amino acids stimulate NO synthase and release NO in the spinal cord, these data suggest that there may be an interaction between nerve terminals containing Glu and SP, and that NO may directly participate in the regulation of synaptic transmission in SP-containing nerve terminals, which may be mediated through the activation of guanylate cyclase and the increase in cyclic GMP levels.
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PMID:Nitric oxide regulates substance P release from rat spinal cord synaptosomes. 759 89

Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11-NH2 residue is replaced by the alpha, gamma-dimethyl, alpha, gamma-dibenzyl and alpha, gamma-di-tert-butyl esters of glutamic acid. These analogues were tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types for agonist and antagonist activity. The dimethyl analogue is a selective full agonist in the NK-1 receptor type and a weak antagonist in the other two receptor types, while the dibenzyl and the di-tert-butyl analogues are potent antagonists in the NK-1 receptor type and weak antagonists in the other two receptor types. It is concluded that appropriate modification at the alpha-carboxamide and the side chain of the methionine residue of substance P may induce antagonism without using D-amino acids.
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PMID:Synthesis of potent antagonists of substance P by modifying the methionyl and glutaminyl residues of its C-terminal hexapeptide and without using D-amino acids. 768 61

Little is known about the functional role of putative neurotransmitters in the nucleus raphe obscurus (NRO) in the control of gastric motor function, although thyrotropin-releasing hormone (TRH) and substance P (SP) have been detected in the cell bodies and/or fibers of this nucleus. Therefore, we investigated the effects of microinjection of these peptides (in a volume of 60 nl) into the caudal NRO of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature motility, and blood pressure. L-Glutamate (30 nmol) was first microinjected into the NRO to identify the "gastric" region of the NRO and elicited significant increases in intragastric pressure as well as pyloric and greater curvature motility in all 16 animals. TRH (2-45 pmol, n = 16) microinjected into the same sites increased intragastric pressure as well as pyloric and greater curvature motility, and these effects were abolished by bilateral cervical vagotomy and atropine (0.5-1.0 mg/kg iv) but not by spinal cord transection. Microinjection of SP (45-405 pmol, n = 15) into the same sites decreased intragastric pressure; however, the inhibitory effect of SP on pyloric and greater curvature motility did not attain statistical significance. The effect of SP on intragastric pressure was completely abolished by bilateral vagotomy but not by systemic administration of atropine (1 mg/kg) or spinal cord transection. Microinjections of 45 pmol TRH and 405 pmol SP just outside of the NRO did not result in changes in gastric function. No overall significant changes in blood pressure were noted after microinjection of L-glutamate, TRH, or SP into the gastric region of the NRO. We conclude that both TRH and SP affect gastric motor function in the caudal NRO via a vagally mediated pathway; TRH apparently activates vagal cholinergic pathways, but the mechanism of SP-evoked gastric motor inhibition remains to be further investigated.
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PMID:Opposing gastric motor responses to TRH and substance P on their microinjection into nucleus raphe obscurus of rats. 769 1

A dose-dependent immunomodulating effect of synthetic low-molecular weight peptides was found in CBA mice. Talcin and its analogue, rigin, tripeptide SKE, substance P and its analogue, and vasopressin were shown to produce an immunostimulating effect, whereas vasopressin tetrapeptide, arginyl-asparagine, and tripeptide SKD showed an immunosuppressive effect. The immunomodulatory effect of the peptides tested was associated with the presence of amino acids such as arginine, lysine, tyrosine, glutamic acid in their chemical structure. These amino acids are essential in the mechanisms of immune responses.
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PMID:[The peptide modulation of immune reactions]. 832 77


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