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)

Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.
 ...
PMID:Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome. 1074 60

Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are intestinal disorders which disrupt normal colonic motility. Enteric tachykinins are well-recognised to play a role in the motor control of the gut, and increased colonic levels of substance P are seen in IBD, whereas decreased levels have been reported in ICC. In this investigation, we have characterised the tachykinin receptor population of normal human colonic circular smooth muscle and examined any changes that occur in IBD and ICC. The selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A(4-10), caused concentration-dependent contractions in healthy tissues; neither NK1 receptor-selective nor NK3 receptor-selective agonists were contractile. In diseased preparations also, only [beta-Ala8]neurokinin A(4-10) caused contractions with EC50 values similar to health. The maximum contractile responses (Emax), however, were significantly decreased in both forms of IBD but significantly increased in ICC. The muscarinic acetylcholine receptor agonist, carbachol, also caused contractions in diseased tissues, but EC50 and Emax values were not significantly different from health. The differential changes in contractility found in IBD and ICC are specific to NK2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders.
 ...
PMID:Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation. 1138 76

1 We presently characterized the tachykinin receptor subtypes, using tachykinin receptor agonists and selective antagonists, that induce submucosal gland fluid flux (J(G)) from porcine tracheal explants with the hillocks technique. We also investigated the effects of the tachykinin receptor agonists on the electrophysiologic parameters of the tracheal epithelium in Ussing chambers. 2 The NK(1) tachykinin receptor agonist substance P (SP, 1 microM) and the NK(3) tachykinin receptor agonist [MePhe(7)]neurokinin B ([MePhe(7)]NKB, 1 microM) induced gland fluid fluxes of 0.29+/-0.03 microl min(-1) cm(-2) (n=26) and 0.36+/-0.05 microl min(-1) cm(-2) (n=24), respectively; while the NK(2) tachykinin receptor agonist [betaAla(8)]neurokinin A (4-10) ([betaAla(8)]NKA (4-10), 1 microM) had no effect on J(G) (n=10). 3 The NK(1) receptor antagonist CP99994 (1 microM, n=9) blocked 93% of the SP-induced J(G), whereas the NK(3) receptor antagonist SB223412 (1 microM, n=12) had no effect on the SP-induced J(G). However, SB223412 (1 microM, n=9) blocked 89% of the [MePhe(7)]NKB-induced J(G) while CP99994 (1 microM, n=10) did not affect the [MePhe(7)]NKB-induced J(G). The NK(2) receptor antagonist SR48968 (1 microM) did not block the J(G) induced by either the NK(1) (n=4) or NK(3) (n=13) receptor agonists. 4 The nicotinic ganglionic acetylcholine receptor antagonist hexamethonium (1 microM) and the muscarinic acetylcholine receptor antagonist atropine (1 microM) also decreased the NK(3) receptor agonist-induced J(G) by 67% (n=10) and 71% (n=12), respectively. 5 The potential difference (PD), short-circuit current (I(SC)), and membrane resistance (R(M)) of the porcine tracheal epithelial membranes were not significantly affected by any of the neurokinin agonists or antagonists (1 microM, basolateral) used in this study, although SP and [betaAla(8)]NKA (4-10) induced a slight transient epithelial hyperpolarization. 6 These data suggest that NK(1) and NK(3) receptors induce porcine airway gland secretion by different mechanisms and that the NK(3) receptor agonists induced secretion is likely due to activation of prejunctional NK(3) receptors on parasympathetic nerves, resulting in acetylcholine-release. We conclude that tachykinin receptor antagonists may have therapeutic potential in diseases with pathophysiological mucus hypersecretion such as asthma and chronic bronchitis.
 ...
PMID:Tachykinin NK3 and NK1 receptor activation elicits secretion from porcine airway submucosal glands. 1252 97

Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeting the potential mechanisms of mucus hypersecretion have been the focus of numerous studies. Conventional expectorants are mainly mucoactive medicines, including nausea-stimulating expectorants, mucolytics, mucokinetics, and proteases and nucleases. In addition, certain traditional Chinese herbal medicines and non-mucoactive agents, including muscarinic acetylcholine receptor antagonists, corticosteroids, leukotriene receptor antagonists and macrolide antibiotics, have also shown expectorant effects. Several novel medicines for expectorant therapy have emerged, including cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids, tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and purinergic agonists. With the increasing number of multidisciplinary studies, the effectiveness of expectorant therapy for the treatment of chronic inflammatory airway diseases has been confirmed. Therefore, the development of novel expectorants and the standardization of expectorant therapy are the direction and focus of future studies, thus benefiting patients who have a chronic inflammatory airway disease.
 ...
PMID:Clinical application of expectorant therapy in chronic inflammatory airway diseases (Review). 2466 26