OBJECTIVEChronic inflammation of airway in bronchial asthma is caused by many complicated elements. Recently, a close attention has been paid to the neurogenic inflammation in airway which is mediated by sensory neuropeptides secreted by sensory nerve in the lung. Neurokinin A (NKA) is an important sensory neuropeptide leading to neurogenic inflammation in airway. Experimental studies showed that NKA has a close relation to asthma. The purpose of the present study was to investigate the changes of NKA in plasma of asthmatic children and possible relationship between sensory neuropeptides and asthma in children.

METHODSThirty-five children with bronchial asthma were studied; 16 of the cases were < 3 yrs and 19 were >or= 3 yrs. Eighteen of the cases had severe asthma and 16 had mild asthma. None of the subjects was treated with glucocorticoid within 3 days before the study started; 15 healthy children without history of asthma or family history of asthma were enrolled as control subjects. Plasma was collected from each case during acute attack of asthma and their clinical remission of the asthmatic children. After purifying with SEP-pak C(18), NKA content was detect by enzyme-linked immunosorbent assay (ELISA) as instructed by the manufacturer of the NKA Kit (NKA unit: ng/L).

RESULTS(1) The content of plasma NKA of asthmatic children was significantly higher at the asthma attack (256 +/- 153) than that at their clinical remission stage (70 +/- 66; q = 9.497, P < 0.01) and than that of the normal control group (38 +/- 6; q = 8.599, P < 0.01); no significant difference in plasma NKA was found between the clinical remission stage and the normal control group (q = 1.245, P > 0.05). (2) There was a significant positive correlation between the asthmatic clinical state and the levels of plasma NKA; the contents of plasma NKA at the stage of acute attack in severe asthma (296 +/- 170) were significantly higher than those of the mild asthmatic children (190 +/- 99; q = 3.77, P < 0.05).

CONCLUSIONSThe contents of plasma NKA were significantly higher during the asthma attack stage of children, and the higher was the level of NKA, the more severe the attack.; with asthma remission, the contents of plasma NKA decreased to normal; the contents of plasma NKA has a close relation to the asthmatic children.

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.

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

BACKGROUND AND OBJECTIVES: Angiotensin -converting enzyme (ACE) inactivates bradykinin, substance P, and neurokinin A, which are thought to play important roles in the pathogenesis of inflammatory diseases. An insertion/deletion (I/D) poly - morphism in the ACE gene was reported to be associated with atopy in a Czech population. MATERIALS AND METHODS: Using the polymerase chain reaction, we investigated the frequencies of the genotypes and alleles of the ACE gene in 137 patients with allergic rhinitis and 498 healthy control subjects. RESULTS: There was no difference in the frequencies of the genotypes in the controls and patients with allergic rhinitis (p>0.05). The D allele was more frequent in patients with allergic rhinitis, but the difference was not statistically significant (p>0.05). CONCLUSION: Our results indicate that I/D polymorphism in the ACE gene is not related to susceptibility to allergic rhinitis in the Korean population.
Alleles ; Angiotensins ; Bradykinin ; Genotype ; Humans ; Neurokinin A ; Polymerase Chain Reaction ; Rhinitis* ; Substance P

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*

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: 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

Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.
Adult ; Dynorphins ; Fertility ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism ; Hypothalamus ; Infertility ; Kisspeptins ; Mammals ; Neurokinin B ; Neuropeptides ; Nutritional Status ; Axis, Cervical Vertebra

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 AND OBJECTIVES: Osteoclasts are the principal cell of bone resorption playing a major role in focal bone erosion associated with cholesteatoma. This study was conducted in order to investigate direct effect of substance P (SP) on osteoclastogenesis and osteoclastic bone resorption in vitro. MATERIALS AND METHOD: SP dose response was measured in receptor activator for NF-kappaB ligand (RANKL)-induced mouse osteoclast culture and osteoclastic bone resorption assay. RT-PCR was performed for the expression of neurokinin(NK) receptor mRNAs in osteoclasts. RESULTS: Treatment with SP (100 nM and 1000 nM) significantly increased osteoclastogenesis. SP (0.1 nM and 1 nM) significantly increased resorption surface area on dentin slices by osteoclasts. Cultured osteoclasts expressed NK-2 receptor mRNA. CONCLUSION: SP has a direct upregulatory effect on osteoclastogenesis and osteoclastic bone resorption that is mediated possibly by NK-2 receptor.
Animals ; Bone Resorption* ; Cholesteatoma ; Dentin ; Mice ; NF-kappa B ; Osteoclasts* ; Receptors, Neurokinin-2 ; RNA, Messenger ; Substance P*