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)

The effects of i.p. administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME) and its inactive isomer, D-NAME, were tested in two nociceptive paradigms in the rat. In the first paradigm, rats were lightly anaesthetized with a mixture of chloral hydrate (120 mg/kg, i.p.) and sodium pentobarbital (20 mg/kg, i.p.). Tail flick reaction times were monitored and thermal hyperalgesia was induced by immersion of the tail in hot water at 55 degrees C for 1.5 min. In the groups of rats pretreated with saline (n = 5), 100 mg/kg D-NAME (n = 6), 10 (n = 5) or 25 (n = 6) mg/kg L-NAME, this thermal injury induced a transient reduction in the reaction time that was 54-59% of the baseline value. However, in the groups of rats pretreated with 50 (n = 6) or 100 (n = 7) mg/kg L-NAME the reaction times were 73.9 +/- 2.7% (P < 0.05) and 102.3 +/- 0.9% (P < 0.001) of the baseline values respectively, indicating a block of the hyperalgesic responses seen in the other groups. As this hyperalgesia has been reported to be blocked by NK-1 receptor antagonists, it is suggested that it is due to the action of endogenous substance P. In the second paradigm, tail flick responses were monitored in the awake rat and thermal hyperalgesia was induced by intrathecal administration of substance P (6.5 nmol) via a chronically implanted catheter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Implication of a nitric oxide synthase mechanism in the action of substance P: L-NAME blocks thermal hyperalgesia induced by endogenous and exogenous substance P in the rat. 852 67

Applying a double-labelling immunofluorescence technique, six types of substance P-containing nerve fibres were distinguished in the human adrenal gland according to the immunohistochemical colocalization of (I) calcitonin gene-related peptide (CGRP), (II) cholecystokinin, (III) nitric oxide synthase, (IV) dynorphin, (V) somatostatin, and (VI) vasoactive intestinal polypeptide. Fibre populations I to IV in their mediator content resembled the respective subpopulations of primary sensory neurons in human thoracic dorsal root ganglia, while populations V and VI revealed no correspondence with dorsal root neurochemical coding. Nerve fibres with the combination substance P/nitric oxide synthase occurred only in the adrenal cortex, whereas all other fibre types were present in both cortex and medulla. As revealed by immuno-electron microscopy, substance P-immunolabelled axon varicosities (a) exhibited synaptic contacts with medullary chromaffin cells or with neuronal dendrites, (b) were directly apposed to cortical steroid cells and (c) were separated from fenestrated capillaries only by the interstitial space. These findings provide immunochemical support for an assumed sensory innervation of the human adrenal gland, and additionally suggest participation of substance P in efferent autonomic pathways. Furthermore, the results are indicative for a differentiated involvement of substance P in the direct and indirect regulation of neuroneuronal and neuroendocrine interactions.
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PMID:Immunohistochemical correlation of human adrenal nerve fibres and thoracic dorsal root neurons with special reference to substance P. 854 49

1. The relative contribution of ETA and ETB receptors in the response of rat skin to endothelins was investigated by use of the selective ETB agonist IRL-1620 and the selective ETA antagonist BQ-123. 2. Binding data suggest the presence of ETA and ETB receptors as preincubation with [Ala3,11,18Nle7]-endothelin-1 reduced ET-1 binding by approximately 40%. 3. Intradermal injection of endothelin-1 (ET-1, 1-10 pmol/site) and ET-3 (3-100 pmol/site) induced a dose-dependent decrease in local blood flow assessed by 133Xe clearance at test sites in rat skin. 4. The endothelin analogue [Ala3,11,18Nle7]-ET-1 (30-1000 pmol/site) induced significant vasoconstriction (P < 0.05) at the highest doses used and the selective ETB receptor agonist, IRL-1620 [Suc[Glu9,Ala11,15] endothelin (8-21)], (0.01-100 pmol/site) acted in a potent manner to induce a significant (P < 0.01) dose-dependent decrease in 133Xe clearance. 5. Co-injection with the selective ETA receptor antagonist, BQ-123 (1 nmol/site), completely abolished the vasoconstriction to ET-1 and partially to ET-3, but had no effect on IRL-1620-induced vasoconstriction. In addition, IRL-1620 responses were not altered at sites treated with submaximal doses of a nitric oxide synthase inhibitor or a prostaglandin synthase inhibitor. 6. ET-1 and IRL-1620 (100 fmol-1 pmol/site) did not induce oedema formation as measured by [125I]-albumin accumulation in the presence or absence of the vasodilator, calcitonin gene-related peptide (CGRP). ET-1 (1-3 pmol/site) inhibited substance P-induced oedema formation and this effect,suggested to be secondary to a vasoconstrictor effect, was significantly reversed by BQ-123 (1 nmol/site).7. The findings in this study indicate that there are ETA and ETB receptors in rat skin and agents which activate either receptor act to mediate a decrease in cutaneous blood flow, but have no effect on increased microvascular permeability.
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PMID:Evidence for ETA and ETB receptors in rat skin and an investigation of their function in the cutaneous microvasculature. 854 85

Previous studies have demonstrated that the epithelium of the respiratory portion of rat nasal mucosa is amply supplied by nerve fibers with immunoreactivities for calcitonin gene-related peptide (CGRP) and substance P (SP), these fibers most likely acting as sensory mediators in the mucosa. The present study demonstrates that some intraepithelial fibers contain a VIP-immunoreactivity whose occurrence in these nerves has previously been neglected. The present study further aims to confirm the occurrence of NO-producing intraepithelial nerve fibers in the rat nasal mucosa and to examine its colocalization with CGRP and with VIP. Double staining methods were used to evaluate the colocalization of NADPH-diaphorase. The reactivity for NADPH-diaphorase and that for CGRP coexisted in only a small part, if any, of the nerve fibers distributed at the basal portion of the epithelium. In the perpendicularly and obliquely oriented transepithelial nerve fibers, both reactivities were clearly demonstrated to be separated in different fibers. VIP immunoreactivity was also present in a part of the intraepithelial nerve fibers of the nasal mucosa, and their entire population was shown to be positive for NADPH-diaphorase. The NADPH-diaphorase-positive reaction was displayed in only a small population of neurons in the trigeminal ganglion, whereas it was seen in numerous neurons in sphenopalatine ganglion, being colocalized with VIP.
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PMID:Intraepithelial nerve fibers in the nasal mucosa of the rat with special reference to the localization of CGRP, VIP and nitric oxide (NO). 856 35

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24-9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24-9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24-9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24-9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24-9981-induced responses. Ro-24-9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24-9981 amplified this response in a specific receptor-mediated fashion.
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PMID:Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch. 856 41

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
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PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

Since it has been demonstrated recently that neuropeptides are involved in wound healing in vivo we investigated the role of substance P (SP), calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in regeneration of ultraviolet (UV) photodamaged rat skin by topical administration of specific antagonists. Topical application of the neurokinin (NK)1-receptor antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabi cyclo[ 2.2.2]octan-3-amine (CP-96,345) significantly delayed the reduction of the necrotic area at all timepoints post UV-irradiation, whereas topically administered NO synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in an increased necrotic area only at 7 days post-irradiation. More important, topically administered L-NAME but not SP reduced nuclear immunolabelling for proliferating cell nuclear antigen (PCNA) of the UV-exposed epidermis, suggesting a NO-mediated stimulation of keratinocyte proliferation. These findings suggest that endogenous SP and NO have a trophic function in wound healing after UV-induced damage of the skin which may be mediated by stimulation of angiogenesis or epidermal cell proliferation.
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PMID:Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. 858 55

The neuroendocrine nature of a subset of Leydig cells has already been established. The present investigation deals with neuroendocrine characteristics of Leydig tumour cells. A number of neuroendocrine and neuronal markers were demonstrated in Leydig cell tumours of 7 men aged 25-41 years. The following substances were immunocytochemically tested in Leydig tumour cells: the monoamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, the indoleamine serotonin, the calcium-binding protein parvalbumin, the microtubule associated protein-2, neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and neuronal nitric oxide synthase (NOS). Compared to the normal interstitial cells beyond the tumours, all neoplastic cells showed a significantly weaker immunoreactivity for nerve cell markers as well as for testosterone and cyclic guanosine monophosphate (cGMP), which is usually accumulated by nitric oxide (NO). This provides evidence for a certain dedifferentiation of Leydig tumour cells. However, these results suggest that tumourous development of Leydig cells does not include loss of neuronal phenotype. Moreover, on the assumption that 'neuronal' Leydig cells exist beside 'non-neuronal' ones in normal testicular tissue, we propose the hypothesis that 'neuronal' Leydig cells can transform to tumour cells.
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PMID:Neuroendocrine characteristics of human Leydig cell tumours. 859 7

Immunohistochemical techniques were used to examine the presence and co-localisation of a range of putative neurotransmitters and other neuronal markers in the myenteric plexus of the small and large intestine of the mouse. Distinct sub-populations of myenteric neurons were identified, based on the combinations of substances they contained and the distribution of their fibres. In the small intestine, there were two major classes of circular muscle motor neurons; one class was characterised by the presence of nitric oxide synthase, vasoactive intestinal peptide plus neuropeptide Y (NOS/VIP/NPY), and the second class contained calretinin plus substance P (CalR/SP). There were seven classes of neurons that innervated myenteric ganglia; these contained nos, vip, nos/vip, npy, calr/calbindin (calb), sp or 5-ht. In the large intestine, there were five major classes of motor neurons that contained nos, nos/vip, gaba, sp, or calr/sp, and seven major classes of neurons that innervated myenteric ganglia and contained nos, vip, calr/calb, calr, sp, gaba or 5-ht. Although some aspects of the patterns of co-localisation are similar to those in other species, this study re-inforces recent analyses that indicate significant species differences in neurochemical patterns in the enteric neurons of different species.
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PMID:Chemical coding of neurons in the myenteric plexus and external muscle of the small and large intestine of the mouse. 860 Dec 95

Nitric oxide is a potent mediator of endothelium-dependent vasodilation, the synthesis of which is catalyzed by the constitutively expressed enzyme endothelial nitric oxide synthase. In this study we have investigated whether human dermal microvascular endothelial cells express endothelial oxide synthase and whether the vasodilator neuropeptides, calcitonin gene-related peptide and substance P, stimulate the release of nitric oxide from these cells. Endothelial nitric oxide synthase was identified by immunohistochemistry in the blood vessels in both the papillary and deep dermis of normal skin, and also in monolayers of human dermal microvascular extracts prepared from both the dermis of normal human skin and human dermal microvascular endothelial cells, a 135-kDa band corresponding to endothelial nitric oxide synthase was identified. Nitric oxide was released from unstimulated human dermal microvascular endothelial cells as assessed by inhibition of platelet aggregation and nitrate formation. Endothelial cell-mediated inhibition of platelet aggregation was blocked by hemoglobin. Calcitonin gene-related peptide, (100 pM to 100 nM) directly inhibited platelet aggregation, and this direct effect was not modulated by microvascular endothelial cells. Substance P (10 nM to 1 muM) and calcitonin gene-related peptide (100 pM to 10 nM) significantly (p<0.05) increased nitrite formation, and this increase was blocked by the competitive nitric oxide synthase antagonist, NG-monomethyl-L-arginine. These results demonstrate that endothelial nitric oxide synthase is expressed in the microvascular endothelium of normal human skin and that human dermal microvascular endothelial cells release nitric oxide constitutively and in response to vasodilator neuropeptides.
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PMID:Neuropeptides induce release of nitric oxide from human dermal microvascular endothelial cells. 861


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