UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present investigation describes the antinociceptive effect of capsaicin in the acetic acid-induced abdominal stretch assay and its mediation by substance P(1-7) fragment [SP(1-7)] and nitric oxide (NO). When injected intrathecally 24 hr before testing, SP(1-7) produced a dose-related decrease in the number of abdominal stretches induced by an i.p. injection of acetic acid. The antinociceptive effect of SP(1-7) (10 nmol) persisted for 62 hr after its injection, a time course that was similar to that produced by a dose of capsaicin (2.6 nmol) that produced an effect of similar magnitude. Antinociception induced by 10 nmol of SP(1-7) was completely reversed by coadministration of 10 nmol of D-SP(1-7); the equivalent antinociception produced by capsaicin was reversed by as small a dose as 1 nmol of D-SP(1-7). The guanylate cyclase inhibitor, methylene blue, at a dose of 10 nmol, prevented both SP(1-7)- and capsaicin-induced antinociception. Capsaicin-induced, but not SP(1-7)-induced, antinociception was prevented by Nw-nitro-L-arginine methyl ester, an NO synthase inhibitor. This inhibition of capsaicin was reversed by coadministration of 120 nmol of L-arginine. Reduced hemoglobin did not prevent capsaicin-induced antinociception. These findings suggest NO is produced and acts within capsaicin-sensitive primary afferent fibers in the dorsal spinal cord to mobilize substance P, resulting in N-terminal induced-antinociception.
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PMID:Substance P N-terminal metabolites and nitric oxide mediate capsaicin-induced antinociception in the adult mouse. 752 54

The possible involvement of the neuropeptides substance P and calcitonin gene-related peptide (CGRP) in the development of neurogenic plasma extravasation in the lower lip, gingiva and incisor pulp was examined in anaesthetized rats by means of the Evans blue method and by using newly developed blockers of substance P (CP-96,345) and CGRP (CGRP8-37). Electrical stimulation of the inferior alveolar nerve (15 V, 2 ms, 10 Hz) for 5 min significantly increased the Evans blue content of the ipsilateral lip, gingiva and pulp by 60 (p < 0.01), 62 (p < 0.01) and 92% (p < 0.05), respectively (n = 8). Pretreatment with CP-96,345 (total dose: 1.5 mg/kg, intravenously) counteracted the dye leakage in the lip and pulp but not in the gingiva (n = 6). The inactive enantiomer (CP-96,344, 1.5 mg/kg, n = 8) or the nitric oxide synthesis inhibitor (N omega-nitro-L-arginine methyl ester hydrochloride, 10 mg/kg, n = 7) did not reduce the stimulation-induced dye extravasation in any of the tissues. Pretreatment with CGRP8-37 (0.3 mg/kg, n = 7) did not significantly influence the development of neurogenic extravasation in the lip and incisor pulp, but it slightly attenuated extravasation in the gingiva. The results indicate that the afferent nerve-induced dye extravasation in the lip and pulp, but not in the gingiva, is to a large extent mediated by substance P acting via neurokinin-1 receptors. There was no evidence for an involvement of nitric oxide or CGRP in neurogenic extravasation in rat incisor and lip.
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PMID:Involvement of substance P but not nitric oxide or calcitonin gene-related peptide in neurogenic plasma extravasation in rat incisor pulp and lip. 752 97

Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolactin-inhibiting activity of dopamine and atrial natriuretic factor.
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PMID:Role of nitric oxide in control of prolactin release by the adenohypophysis. 752 11

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.
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PMID:Nitrinergic and peptidergic innervation of the human oesophagus. 753 Feb 28

The present study determined the participation of different endogenous mediators in adaptive cytoprotection against gastric gland damage caused by ethanol in rabbits. Using the isolated gland preparation, pretreatment with 10(-5)M of either indomethacin, Nw-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM), but not of substance P antagonist, intensified the 10% (v/v) ethanol-induced gastric gland damage and lessened the degree of cytoprotection evoked by 2% (v/v) ethanol to a significant level. Co-administration with 10(-4)M of prostaglandin E2, L-arginine or glutathione to the respective groups completely reversed the above adverse effects. These results demonstrate the involvement of endogenous prostaglandins, nitric oxide and glutathione in gastric adaptive cytoprotection against the damaging action of ethanol in the rabbit gastric glands.
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PMID:Endogenous mediators in adaptive cytoprotection against ethanol-induced gastric gland damage in rabbits. 753 Mar 12

1. This study investigated tachykinin-evoked vasodilatation in the microvasculature of the hamster cheek pouch in vivo. Arterioles and venules were observed by intravital microscopy with video recording, and vasodilatation and constriction, defined as changes in blood vessel diameter, measured by image analysis. All agents were applied topically by superfusion. None of the agents tested had a significant effect on venule diameter. 2. When arterioles were preconstricted (by ca. 50%) with endothelin-1 present in the superfusing medium, substance P (0.3-30 nM) was a potent vasodilator, being 10 fold more active than both neurokinin A and the NK1 receptor-selective agonist, substance P methyl ester. The NK2 receptor-selective agonist, [beta-Ala8]-NKA(4-10)(0.1-10 microM) was active only at high concentrations, and the NK3 receptor-selective agonist senktide (0.1-10 microM) was virtually inactive (n = 8 hamsters). Dilatation evoked by tachykinins and analogues was rapid in onset (< 0.5 min) and readily reversible. 3. At low concentrations (1-10 nM), the non-peptide tachykinin NK1 receptor antagonist SR140333 ((S)1-(2-[3(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)pi peridin-3- yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octone, chloride) had no effect on the diameter of preconstricted arterioles per se, but potently inhibited dilator responses to substance P methyl ester (apparent pKB 9.9 +/- 0.2; n = 5 hamsters, n = 10 estimates). SR140333 (10 nM) did not inhibit submaximal dilator responses evoked by human alpha calcitonin gene-related peptide (alpha CGRPh; 1.0 nM; P > 0.05; n = 5). 4 The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 microM) caused a51.3 +/- 5.4% arteriolar constriction. In the presence of L-NAME, submaximal vasodilator responses to substance P (10-I00 nM) and carbachol (0.1-1.0 microM) were significantly attenuated (n = 5 hamsters;P<0.05) as compared to responses obtained in preparations that were preconstricted to a similar extent by endothelin-l (48.0 +/- 5.6%). L-NAME (10 M) was without effect on submaximal vasodilator responses to alpha CGRPh (0.1 nM) or sodium nitroprusside (1O nM) (n = 5 hamsters; P> 0.05).5 We conclude that tachykinin-evoked arteriolar vasodilatation in the hamster cheek pouch is mediated via NK, receptor activation and depends, at least in part, on the release of nitric oxide. The NKI receptors mediating vasodilatation can be blocked by topical application of SR140333; which may therefore be useful in the investigation of the role of NK1 receptors in neurogenic inflammation in the microvasculature.
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PMID:Inhibition by SR 140333 of NK1 tachykinin receptor-evoked, nitric oxide-dependent vasodilatation in the hamster cheek pouch microvasculature in vivo. 753 May 73

Recent studies demonstrate that nitric oxide and cyclic guanosine 3',5'-monophosphate may mediate hyperalgesia induced by N-methyl-D-aspartate at the level of the spinal cord. One possible mechanism for this action is that nitric oxide increases transmitter release from the primary afferent nociceptors that synapse in the dorsal horn of the spinal cord. To address this possibility, we investigated whether various nitric oxide donors and cyclic guanosine 3',5'-monophosphate could alter the release of substance P and calcitonin gene-related peptide from rat sensory neurons in culture. Sodium nitroprusside (100 nM to 100 microM) had little effect on basal release of either peptide, but it significantly increased the release of substance P and calcitonin gene-related peptide induced by 50 nM capsaicin. In contrast, sodium nitroprusside did not alter release evoked by 100 nM bradykinin or 30 mM KCl. Two other nitric oxide-donating compounds, S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine did not enhance resting or capsaicin-evoked peptide release, although they induced a marked elevation in the intracellular cyclic guanosine 3',5'-monophosphate levels. Pretreating the cultures with 8-bromo-cyclic guanosine 3',5'-monophosphate, (0.5 or 0.1 mM for 30 or 60 min) did not result in the enhancement of capsaicin-induced release from sensory neurons. Moreover, pretreating the cells with the nitric oxide synthase inhibitor, NG-nitro-L-arginine (100 microM), abolished the rise in cyclic guanosine 3',5'-monophosphate induced by capsaicin without altering capsaicin-stimulated release of either peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide and cyclic guanosine 3',5'-monophosphate do not alter neuropeptide release from rat sensory neurons grown in culture. 753 4

Nitric oxide and various neuropeptides in the myenteric plexus regulate esophageal motility. We sought colocalization of nitric oxide synthase and neuropeptides in frozen sections of mid-portion of smooth-muscled opossum esophagus using NADPH-diaphorase activity to mark the synthase and immunoreactivity to detect peptides. The peptides, all with demonstrated physiological activity in this organ, were calcitonin gene-related peptide, galanin, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. The ExtrAvidin Peroxidase immunostain for each peptide was carried up to the final peroxidase reaction with 3-amino-9-ethyl-carbazole. The NADPH-diaphorase reaction was applied with short incubation to provide light staining just before the peroxidase reaction was performed. We examined sections for the proportions of singly and dually labeled nerve cells in the myenteric plexus. NADPH-diaphorase activity was highly colocalized with calcitonin gene-related peptide (59%), galanin (54%), and vasoactive intestinal polypeptide (53%). It showed little colocalization with neuropeptide Y (10%) and substance P (8%). The proportions of all nerve cells containing each of the substances were: NADPH-diaphorase--33%, calcitonin gene-related peptide--30%, galanin--55%, neuropeptide Y--16%, substance P--35%, and vasoactive intestinal polypeptide--58%. We conclude that the nerves responsible for peristalsis in the esophagus may act by releasing nitric oxide along with other inhibitory substances, calcitonin gene-related peptide, galanin, and vasoactive intestinal polypeptide, but not excitatory substances, neuropeptide Y and substance P.
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PMID:Colocalization of NADPH-diaphorase activity and certain neuropeptides in the esophagus of opossum (Didelphis virginiana). 753 20

The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both L-NAME (100 mg/kg IV, P < .05) and 7-NI (10 mg/kg IV, P < .05) caused an L-arginine (100 mg/kg IV, P < .01)-reversible inhibition of neurogenic edema as measured by 125I-albumin accumulation, whereas D-NAME (inactive enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicted vasopressor effect (before, 115 +/- 18 mm Hg; 5 minutes after, 174 +/- 18 mm Hg; n = 6; P < .05), whereas 7-NI showed no significant increase in blood pressure (before, 96 +/- 9 mm Hg; 5 minutes after, 102 +/- 10 mm Hg; n = 6), and neither L-NAME nor 7-NI had any effect on basal or vasodilator calcitonin gene-related peptide (CGRP, 10 pmol per site)-stimulated local blood flow in rat skin, as measured by laser Doppler flowmetry. Furthermore, systemic and local 7-NI had no effect on edema formation induced by local administration of substance P (with or without CGRP) and histamine (with or without CGRP) in rat skin. Since 7-NI blocks edema produced by stimulation of the saphenous nerve, it is suggested that release of NO is involved in neurogenic edema formation, but the vasodilator action of NO is unimportant in this context.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential role for nitric oxide in neurogenic inflammation in rat cutaneous microcirculation. Evidence for an endothelium-independent mechanism. 753 19

The role of nerve-induced release of nitric oxide (NO) as a modulator of neuroeffector transmission was studied in the longitudinal muscle of the guinea pig colon. The biological activity of a vascular relaxing factor released by nerve stimulation was examined in a bioassay cascade system. Furthermore, biochemical measurements of nerve-induced release of the NO metabolite nitrite (NO2-) were made with a chemiluminescence technique. Transmural nerve stimulation elicited contractile responses that were partly blocked by atropine and further inhibited after additional application of the tachykinin receptor antagonist CP-96, 345. The NO-synthase inhibitor N omega-nitro-L-arginine (NOARG) enhanced the nerve-induced contractions and concomitantly increased the basal degree of contraction ('tone'). The relaxations obtained by nerve stimulation after treatment with atropine and histamine were inhibited by NOARG. Electrical stimulation of the guinea pig colon released a non-adrenergic non-cholinergic (NANC) vascular relaxing factor into the tissue superfusate. The half-life of this factor down the cascade was the same as that observed with exogenous application of NO NOARG and tetrodotoxin (TTX) inhibited the release of the relaxing factor. During transmural nerve stimulation there was a significant increase in NO/NO2- release. This increase was inhibited by TTX and N omega-nitro-L-arginine methyl ester (L-NAME). In conclusion, pharmacological analysis as well as bioassay and biochemical measurements suggest that NO is released during nerve stimulation in the guinea pig colon, where it mediates smooth muscle relaxation.
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PMID:Nitric oxide-like activity in guinea pig colon as determined by effector responses, bioassay and chemiluminescence analysis. 753 96

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