OBJECTIVETo investigate the effects of substance P on cultured rat osteoclasts.

METHODSNeurokinin-1 (NK1) receptor expression in osteoclasts was examined by immunohitochemical method, and changes of bone resorption activity caused by substance P and NK1 receptor antagonists were detected by pit formation assay.

RESULTSImmunoreactivity for NK1 receptor was distributed in the cytoplasm of osteoclasts. The average of pit formation areas significantly increased with addition of substance P (10(-7)-10(-4) mol/L) (P < 0.05), but the number of pitformations did not change (P > 0.05). NK1 receptor antagonists inhibited the enhancement of the bone resorption by substance P addition.

CONCLUSIONThe findings suggested that substance P may stimulate osteoclasts and result in bone resorption by the mediation of NK1 receptor.

Animals ; Osteoclasts ; Rats ; Receptors, Neurokinin-1 ; Substance P

OBJECTIVE: In inflammation, hyperalgesia is a common phenomenon but its mechanism has not been clarified. Recently some reports suggested substance P might be important factors for inflammatory hyperalgesia in somatic tissue. This study was performed to see whether substance P modulate the activities of uterine afferent fibers in the hypogastric nerve of the cat. METHODS: While recording the electrical activities of nerve fibers, mechanical stimuli were applied as balloon distention using balloon inserted into uterine lumen before and during substance P infusion through uterine artery. RESULTS: Substance P increased the responses to balloon distension of uterus in 14 uterine mechanoreceptive afferent fibers of 24 over 10% compared to before substance P infusion, and decreased the responses of 3. And L-703,606, the neurokinin 1 receptor antagonist failed the modulation of mechano sensitive response by substance P and reduced the spontaneous activities. CONCLUSIONS: These results suggest that substance P modulated the activities of uterine nerve fibers and their responses to mechanical stimulus. It is hypothesized that this kind of modulation of afferent nerve fibers by substance P may be important for the development of inflammatory hyperalgesia.
Animals ; Cats ; Hyperalgesia ; Inflammation ; Mechanoreceptors* ; Nerve Fibers ; Receptors, Neurokinin-1 ; Substance P* ; Uterine Artery ; Uterus

The pre-Bötzinger complex (pre-BötC) residing in the ventrolateral medulla oblongata, is thought to be the kernel of respiratory rhythmogenesis. Episodic hypoxia exerts respiratory long-term facilitation, being recognized as electrophysiological characteristic of respiratory motor neuroplasticity. Our previous study demonstrated up-regulated expression of phospho-protein kinase C θ (P-PKCθ) in the pre-BötC of rats receiving chronic intermittent hypoxic (CIH) challenge. The present study was aimed to examine subcellular distribution of P-PKC substrates (P-PKCsub) and explore PKC down-stream targeting proteins in the pre-BötC in normoxic and CIH rats. Using neurokinin-1 receptor (NK1R) as a marker of the pre-BötC, P-PKCsub immunoreactivity was revealed by immunofluorescence and immuno-electron microscopic double-labeling in the pre-BötC. Western blot was applied to analyze P-PKCsub proteins in ventrolateral medulla, containing the pre-BötC. The results showed that NK1R immunoreactivity (NK1R-ir) was expressed mainly along plasma membranes of somata and processes, outlining pre-BötC neurons under the light microscope. P-PKCsub immunoreactive (P-PKCsub-ir) fluorophores in dot-like appearance appeared in somata and processes. Some were in close apposition to plasma membranes. A majority of P-PKCsub-ir neurons was found with NK1R-ir. CIH challenge up-regulated the expression of P-PKCsub proteins in the ventrolateral medulla. Under the electron microscope, NK1R-ir product was found to distribute along the inner membrane surfaces of somata and dendrites. P-PKCsub-ir gold particles were located in somata and dendrites, and some were distributed along the inner membrane surfaces, as well as in the endoplasmic reticulum and postsynaptic dense body. These results suggest that CIH challenge up-regulates the expression of P-PKCsub proteins, probably including some receptor proteins in the postsynaptic membrane, which may contribute to respiratory neuroplasticity via activation of PKCθ in the pre-BötC.
Animals ; Hypoxia ; Medulla Oblongata/metabolism* ; Neurons/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurokinin-1/metabolism*

BACKGROUND: 5-HT3 receptor antagonist, dexamethasone and droperidol were used for the prevention of postoperative nausea and vomiting (PONV). Recently, neurokinin-1 (NK1) antagonist has been used for PONV. We evaluated the effect of oral aprepitant premedication in addition to ondansetron. METHODS: A total 90 patients scheduled for elective rhinolaryngological surgery were allocated to three groups (Control, Ap80, Ap125), each of 30 at random. Ondansetron 4 mg was injected intravenously to all patients just before the end of surgery. On the morning of surgery, 80 mg and 125 mg aprepitant were additionally administered into the Ap80 group and Ap125 group, respectively. The rhodes index of nausea, vomiting and retching (RINVR) was checked at 6 hr and 24 hr after surgery. RESULTS: Twelve patients who used steroids unexpectedly were excluded. Finally 78 patients (control : Ap80 : Ap125 = 24 : 28 : 26) were enrolled. Overall PONV occurrence rate of Ap125 group (1/26, 3.9%) was lower (P = 0.015) than the control group (7/24, 29.2%) at 6 hr after surgery. The nausea distress score of Ap125 group (0.04 +/- 0.20) was lower (P = 0.032) than the control group (0.67 +/- 1.24) at 6 hr after surgery. No evident side effect of aprepitant was observed. CONCLUSIONS: Oral aprepitant 125 mg can be used as combination therapy for the prevention of PONV.
Dexamethasone ; Droperidol ; Humans ; Morpholines ; Nausea ; Ondansetron ; Postoperative Nausea and Vomiting ; Premedication ; Receptors, Neurokinin-1 ; Receptors, Serotonin, 5-HT3 ; Steroids ; Vomiting

OBJECTIVE: To find out wheather the substance P takes part in the pain mediating system of uterus, and to ascertain the role of substance P in the hypersensitivity of hypogastric nerve to bradykinin during the uterine inflammation. METHODS: The uterus has two sensory innervations, which are the hypogastric nerve and the pelvic nerve. Since the hypogastric nerve is known to show increased sensitivity to bradykinin, a pain mediator, when the uterus is in inflammatory state, the hypogastric nerve recording was done for electrophysiological study of uterine pain-mediating mechanism in female SD rats (200-250 g). NK1 receptor antagonist (L-703,606) was injected through uterine artery before injecting bradykinin while uterus was under inflammation. RESULTS: The NK-1 receptor antagonist (L-703,606) decreased the spontaneous nerve impulse during inflammation, and it also decreased the hypersensitivity of the hypogastric nerve to bradykinin during the uterine inflammation. CONCLUSION: Substance P mediates the pain sense of hypogastric nerve, and it also plays a role in increased sensitivity of hypogastric nerve to bradykinin while uterus is in inflammatory state.
Action Potentials ; Animals ; Bradykinin* ; Female ; Humans ; Hypersensitivity ; Inflammation ; Mustard Plant* ; Negotiating ; Rats* ; Receptors, Neurokinin-1* ; Substance P ; Uterine Artery ; Uterus*

BACKGROUND: To identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn. METHODS: In experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan's surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining. RESULTS: In experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group. CONCLUSIONS: Systemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management.
Animals ; Extremities ; Hyperalgesia ; Pain, Postoperative ; Pregnanolone ; Rats ; Receptors, Neurokinin-1 ; Spinal Cord ; Spinal Cord Dorsal Horn ; Substance P ; Weight-Bearing

BACKGROUND AND OBJECTIVES: In airway tissues, the substance P has been suggested as the neurotransmitter in the afferent sensory nerve which responds to various irritants and that it may be involved in airway allergic reactions. Neurokinin 1 receptor exhibits preferential affinity for the substance P. In contrast to the substance P, neurokinin 1 receptor has not been examined at the protein level in nasal mucosa with allergic rhinitis. The purpose of this study was to investigate the localization and distribution of the neurokinin 1 receptor in the nasal mucosa of normal subjects and allergic rhinitis subjects. MATERIALS AND METHOD: Biopsy specimens were collected from 10 normal control subjects and 10 allergic rhinitis subjects and were immunostained for the neurokinin 1 receptor. Expressions of neurokinin 1 receptor were quantified through a light microscope. RESULTS: Neurokinin 1 receptor was localized at the epithelium, inflammatory cells, vascular endothelial cells, and glandular cells in the nasal mucosa of both normal subjects and allergic rhinitis subjects. When comparing the distributions of normal nasal mucosa and neurokinin 1 receptor, the neurokinin 1 receptor was significantly increased in the epithelial cell layer of allergic rhinitis, but there was no difference in the submucosa between two groups. CONCLUSION: These results show that neurokinin 1 receptor in the nasal epithelial cells may play an important role in the pathogenesis of hyper-reactivity in allergic rhinitis.
Biopsy ; Endothelial Cells ; Epithelial Cells ; Epithelium ; Hypersensitivity ; Irritants ; Nasal Mucosa ; Neurotransmitter Agents ; Receptors, Neurokinin-1* ; Rhinitis* ; Substance P

BACKGROUND/AIMS: Male predominance has been observed in the erosive reflux disease (ERD), but reverse finding in nonerosive reflux disease (NERD). This suggests sex-specific medicine approach is needed but its mechanism is remained to be elucidated. We aimed to compare clinical characteristics and mRNA expression levels of tight junction-related proteins between male and female gastroesophageal reflux disease (GERD). METHODS: Sixteen healthy controls, 45 ERD, and 14 NERD patients received upper endoscopies and completed questionnaires. Quantitative real-time polymerase chain reactions of occludin (OCLN), zonal occludens (ZO) 1, claudin-1 (CLDN1) and claudin-4 (CLDN4), and neurokinin 1 receptor (NK1R) were performed in the distal esophageal mucosal specimen. These results were analyzed by sex. RESULTS: Female GERD patients were affected more by reflux symptoms than males. The impairment of overall quality of life was more prominent in female patients with reflux symptoms than male patients (5.6±0.2 vs 4.9±0.6, p=0.009). The levels of OCLN mRNA expression were significantly lower in the male ERD group. On the other hand, those of CLDN1, CLDN4, and NK1R except ZO-1 were significantly higher in the male ERD group. CONCLUSIONS: We demonstrated that female ERD/NERD patients were affected more by GERD and male ERD patients showed significant changes of tight junction protein mRNA expression levels.
Claudin-1 ; Claudin-4 ; Female* ; Fluconazole ; Gastroesophageal Reflux* ; Hand ; Humans ; Male* ; Occludin ; Polymerase Chain Reaction ; Quality of Life ; Receptors, Neurokinin-1 ; RNA, Messenger* ; Tight Junction Proteins ; Tight Junctions*

OBJECTIVETo investigate the preventive and therapeutic effects of Xiaobanxia Fuling Decoction (XBFD) on cisplatin-induced pica rats and to study its mechanism.

METHODSForty-two male Sprague-Dawley rats were randomly divided into the following 7 groups, i.e., the blank control group, the model group, the high-, middle-, and low-dose XBFD groups (at the daily dose of 30, 15, and 7. 5 g/kg, respectively), the aprepitant (at the daily dose of 13 mg/kg), and pure Chinese medicine group (at the daily dose of XBFD 15 g/kg), 6 in each group. On the 3rd day of this study, 3 mg/kg cisplatin was intraperitoneally injected to rats except the blank control group and the model group to establish the pica rat model. The consumptions of kaolin, food, and the general situation of rats were observed. The protein and mRNA expressions of neurokinin 1 receptor (NK1R) in both the medulla oblongata and the gastric antrum were measured by immunohistochemical assay and Real-time fluorescent quantitative PCR respectively on the sixth day of this study.

RESULTSOn the third, fourth, and fifth day of this study, the consumption of kaolin of rats significantly increased when compared with the blank control group (P<0.01). Compared with the model group, the consumption of kaolin significantly decreased in the high-, middle-, and low-dose XBFD groups on the third, fourth, and fifth day of this study (P<0.05). The food intake of rats in the high-dose XBFD groups significantly increased when compared with the model group on the third day of this study (P<0.05). The protein and mRNA expressions of NK, R in the medulla oblongata and the gastric antrum significantly decreased in the high- and middle-dose XBFD groups when compared with the model group (P<0.05).

CONCLUSIONSXBFD could prevent and treat cisplatin-induced pica in rats. Its effect might be correlated with decreasing expressions of NK, R in the medulla oblongata and the gastric antrum.

Animals ; Cisplatin ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Pica ; chemically induced ; drug therapy ; prevention & control ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurokinin-1 ; metabolism

OBJECTIVETo explore the relationship between neuropeptide substance P (SP) and wound healing in scalded rats.

METHODS(1) Scalded rats with different degrees of scald injury were employed as the experimental model and were sacrificed at 24 post scald hour (PSH), and on 3, 7 and 14 post scald days (PSD). The SP content in the wound was detected with radioimmunoassay method. (2) The murine granulation tissue fibroblasts (GTF) were cultured with different culture media, and divided into control, SP and Spantide (SP receptor antagonism) groups. The effects of SP and Spantide on the cellular activity and apoptotic rate of murine GTF were assessed in vitro.

RESULTSThere was significant difference of the SP content among the superficial (145 +/- 78) ng/g, partial (94 +/- 48 ng/g) and full thickness (53 +/- 27 ng/g) scald wounds at 24 PSH (P < 0.01), while the SP content in partial thickness burn wound on 3 and 7 PSD obviously increased; and that in deep partial thickness burn wound obviously increased on 7 and 14 PSD. But the SP content remained unchanged in full thickness scald wound. (2) SP could promote the activity of GTF and inhibit its apoptosis (The GTF activity in control, SP groups were 0.21 +/- 0.05, 0.36 +/- 0.07, respectively, P < 0.01). Spantide could inhibit the interaction between SP and GTF.

CONCLUSIONSP can promote GTF proliferation, and the SP content in wound is closely associated with the depth of the injury and wound healing capacity.

Animals ; Burns ; metabolism ; pathology ; Cell Proliferation ; Disease Models, Animal ; Female ; Fibroblasts ; cytology ; Male ; Rats ; Rats, Wistar ; Receptors, Neurokinin-1 ; metabolism ; Substance P ; analogs & derivatives ; pharmacology ; Wound Healing