Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.
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PMID:The effects of topical doxepin on responses to histamine, substance P and prostaglandin E2 in human skin. 934 34

Histologically, acupuncture points show neuronal innervation. One hundred seventy-seven tissue samples of acupuncture points and control points from 4 dogs were collected. Concentrations of substance P, a neurotransmitter, in the skin, muscle and subcutis of acupuncture points and control points were measured by means of enzyme immunoassay. The determined tissue concentrations of substance P (mean +/- SEM) in acupuncture points and control points were 1.81 +/- 0.13 and 1.51 +/- 0.1 ng/g in the muscle, 3.33 +/- 0.29 and 2.63 +/- 0.28 ng/g in the skin and 1.59 +/- 0.22 and 1.32 +/- 0.16 ng/g in the subcutis, respectively. The results indicate that there is a difference in the neurochemical profile between acupuncture points and control points.
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PMID:Comparison of substance P concentration in acupuncture points in different tissues in dogs. 959 89

We have examined the short-term effects of three volatile anaesthetics, halothane, isoflurane and desflurane, on mucociliary activity in the rabbit maxillary sinus in vivo. Mucociliary activity was recorded photoelectrically and the signal processed by fast Fourier transformation. Administration of 1.0 MAC of halothane, isoflurane or desflurane caused a temporary increase in mucociliary activity, with mean peak responses of 47.8 (SEM 13.0)%, 44.0 (9.6)% and 45.1 (23.7)% (n = 6), respectively. The response to all three compounds was biphasic; an initial peak was observed within 2 min and a second peak at 3-8 min. The second response was not significant for halothane. In contrast, desflurane produced a significant second peak while the first was small and failed to reach significance. Halothane displayed an initial peak within 2 min which was blocked by atropine but not by the neurokinin 1 (NK1) receptor antagonist CP-99. The second peak at 3-5 min was less pronounced for halothane than for isoflurane or desflurane. The second peak was not affected by atropine pretreatment, but was blocked by pretreatment with CP-99. A combination of atropine and CP-99 pretreatment abolished the mucociliary response to halothane. Atropine pretreatment did not affect, whereas CP-99 significantly reduced, the response to desflurane. We conclude that the NK1-mediated response was most pronounced for desflurane which is considered the most airway irritating compound of the three. It is likely that the size of the NK1-mediated response reflects the airway-irritating properties of the volatile anaesthetic used.
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PMID:Changes in mucociliary activity may be used to investigate the airway-irritating potency of volatile anaesthetics. 964 Jan 54

Inhalation of neurokinin (NK) A causes bronchoconstriction in patients with asthma. The NKA-induced bronchoconstriction in isolated human airways is mediated via the NK2 receptor and inhibited by SR 48968, a potent and specific nonpeptide tachykinin NK2 receptor antagonist. In the present study, the effect of orally administered SR 48968 on NKA-induced bronchoconstriction was examined in 12 mild asthmatics. On the screening day and during the study periods, increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol x mL(-1)) were inhaled, until the forced expiratory volume in one second (FEV1) and specific airway conductance (sGaw) decreased by at least 20 and 50%, respectively. During the study periods, 100 mg SR 48968 or matched placebo was ingested in a double-blind, randomized, crossover fashion and NKA provocation was performed at 1.5 and 24 h after dosing. At 1.5 h, the mean (SEM) log10 provocative concentration of NKA causing a 20% fall in FEV1 (PC20 FEV1) was -6.25 (0.20) after SR 48968 and -6.75 (0.17) after placebo (p=0.05); the mean log10 provocative concentration of NKA causing a 35% fall in sGaw (PC35 sGaw) was -7.02 (0.28) after SR 48968 and -7.64 (0.19) after placebo (p=0.05). At 24 h, the mean log10 PC20 FEV1 was -6.21 (0.17) after SR 48968 and -6.65 (0.11) after placebo (p=0.05); the mean log10 PC35 sGaw was -6.85 (0.23) after SR 48968 and -7.17 (0.15) after placebo (nonsignificant). As PC20 FEV1 and/or PC35 sGaw were not reached in up to 4 patients per SR 48968 group, the differences between SR 48968 and placebo were underestimated. In conclusion, oral treatment with 100 mg SR 48968 caused a significant inhibition of neurokinin A-induced bronchoconstriction in asthmatics. This finding constitutes the first evidence of inhibition of sensory neuropeptide-induced bronchoconstriction by a selective tachykinin receptor antagonist in humans.
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PMID:The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics. 970 8

The neurohormonal control of the migrating motor complex (MMC) is not fully understood. The hypothesis of the present study was that neuropeptide levels might vary with the different phases of the MMC and that a similar variation might be found in the secretions of the gastrointestinal tract. Thus, plasma and intraduodenal concentrations of vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and neurokinin A (NKA) were determined by radioimmunoassay every 10 min during two complete MMC cycles in eight male subjects. For comparison, plasma motilin (MOT) concentrations were measured. Plasma concentrations of MOT (mean peak value +/- SEM; 39 +/- 6 pmol L-1), but none of the neuropeptides studied, showed a cyclic variation in plasma with the different phases of the MMC. Peak intraduodenal concentrations of VIP (79 +/- 23 pmol L-1), SOM (2437 +/- 432 pmol L-1) and SP (718 +/- 326 pmol L-1) occurred at or at the time point before the onset of phase III of the MMC. No such correlation was observed for NKA. These results demonstrate that intraduodenal but not plasma concentrations of the neuropeptides VIP, SOM and SP show an association with phase III of the MMC. The biological relevance of this finding is yet unclear, but the results raise the possibility that gut neuropeptides may regulate fasting motility through a luminal release.
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PMID:Intraduodenal neuropeptide levels, but not plasma levels, vary in a cyclic fashion with the migrating motor complex. 985 20

Aging in women is associated with dramatic changes in neuronal morphology and neuropeptide gene expression in the medial basal hypothalamus. There is hypertrophy of neurons expressing substance P and neurokinin B gene transcripts in the infundibular (arcuate) nucleus, accompanied by increased tachykinin gene expression. In addition, gonadotropin-releasing hormone (GnRH) gene expression is increased in a separate subpopulation of neurons within the medial basal hypothalamus. In contrast, the number of neurons expressing proopiomelanocortin (POMC) mRNA in the infundibular nucleus of older women is decreased. To determine whether neuronal degeneration contributes to these phenomena, unbiased stereologic methods were used to compare the total number of infundibular neurons between groups of young (premenopausal) and older (postmenopausal) women. There was no significant difference in the total number of infundibular neurons between young (520,000 +/- 42,000 neurons, mean +/- SEM) and older women (505,000 +/- 51,000 neurons, mean +/- SEM). The mean volume of neuronal somata, however, was increased by 40% in the older women (young, 1,860 +/- 180 microm(3) vs. older, 2,610 +/- 230 microm(3), mean +/- SEM, P < 0.05). These data demonstrate that neuronal hypertrophy in older women is not accompanied by degeneration of the infundibular nucleus. We conclude that the loss of menstrual cyclicity in middle-aged women cannot be explained by loss of neurons within the hypothalamic control center for reproduction.
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PMID:Stereologic study of the hypothalamic infundibular nucleus in young and older women. 1093 89

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.
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PMID:Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins. 1112 9

Neutral endopeptidase (NEP) is described in airways as the major degrading enzyme of tachykinins such as neurokinin A (NKA) and substance P (SP). Due to its localization and mode of action NEP may play a role in the pathophysiology of bronchial reactivity (BR) especially under the aspect of neurogenic inflammation. Serum NEP concentrations were measured by ELISA to investigate if there is a correlation between serum NEP and the degree of bronchial reactivity expressed by PC20-FEV1 histamine(.). PC20-FEV1 histamine was determined in 31 asthmatic patients [age 31.9+/-1.3 years (mean+/-SEM) FEV1=92.1+/-2.4% (mean+/-SEM) 16 females/15 males]. Prior to the histamine challenge blood samples were obtained and stored at -70 degrees C until determination using ELISA. A significant correlation between serum NEP and the PC20-FEV1 (n=31, r=0.49, P<0.01) was found. The results suggest that serum NEP is modulating neuropeptide-induced effects in the pathophysiology of airway responsiveness.
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PMID:Correlation between neutral endopetidase (NEP) 3.4.24.11 in serum and the degree of the bronchial hyperreactivity. 1116 54

Since serotonin (5-HT) is implicated in exacerbating acute coronary syndromes, we studied the reactivity of atrial coronary arterioles (70-140 microm) of atherosclerotic patients undergoing cardiac surgery to 5-HT, substance P (Sub P), and sodium nitroprusside by video-microscopy. Before ischemia, 5-HT-induced relaxation was not affected by NS398 (cyclooxygenase inhibitor), H2O2 or U63557A (thromboxane A2 synthase inhibitor), but was reduced by L-NNA. 5-HT elicited a potent contractile response after ischemia that was inhibited by NS398, Indo, and U63557A. While Sub P relaxation was decreased after ischemia, SNP relaxation was unchanged. The mRNA steady-state levels of NOS-3, NOS-2, prostacyclin synthase, and COX- 1 were not altered by ischemia. COX-2 mRNA and protein levels (Westernblotting), however, were increased (mean +/- SEM) 2.4 +/- 0.4 and 3.2 +/- 0.7 fold, respectively, in ischemic atrium corroborating with the immunohistochemistry of atrial tissue. It is concluded that myocardial ischemia enhanced contractile response of coronary arterioles to 5-HT maybe due to the stimulated prostaglandin release (likely thromboxane A2) secondary to induction of COX-2 expression. These findings may have implications regarding the cause of coronary spasm during acute myocardial ischemia.
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PMID:Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. 1121 33

The agonist activity of substance P (SP) is a function of the C-terminal domain of the peptide. A C-terminal SP fragment (SP(6-11)) and analog (septide) and neurokinin A (NKA; a related tachykinin with a divergent N-terminal amino acid sequence) were found to be full neurokinin-1 receptor (NK-1R) agonists, but were not able to desensitize the receptor maximally as much as SP. Substance P caused 95.6 +/- 0.9% maximal desensitization of the NK-1R whereas SP(6-11), septide, and NKA(only)caused 74 +/- 3.5, 50.6 +/- 8, and 71.5 +/- 4.4% maximal desensitization, respectively (mean +/- SEM; P < 0.001 vs SP). When a series of SP C-terminal fragment peptides were tested for their NK-1R desensitizing activity, it was found that SP(5-11)and SP(6-11)caused significantly less maximal NK-1R desensitization than SP. SP N-terminal fragment peptides had no effect on the ability of SP(6-11)to compete with(3)H-SP binding, generate an IP(3)response, or cause NK-1R desensitization when tested with or without SP(6-11). SP, SP(6-11), septide, and NKA all maximally stimulated 8-9-fold increases in NK-1R phosphorylation. When attached to the C-terminal domain of SP responsible for NK-1R binding and agonism, the N-terminus of SP is responsible for 25-50% of homologous desensitization and this may occur via a mechanism other than NK-1R phosphorylation.
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PMID:The N-terminal domain of substance P is required for complete homologous desensitization but not phosphorylation of the rat neurokinin-1 receptor. 1134 7


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