title: Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure.
abstract: This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1 and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in rats; and 2) determine if pretreatment with antioxidants ameliorates the deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP-96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30-120 min. Rats were killed 0-8 h later. Total lung resistance (RL), airway smooth muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP concentrations, and reactive oxygen species formation [via lucigenin- and luminal-amplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP concentrations increased significantly in nonpretreated rats following OSE in a dose-dependent manner. RL and total ASMA increased over time after OSE. Vitamin C and catechin pretreatments were associated with significantly reduced lucigenin CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced following 60 and 120 min of OSE in catechin- and CP-96345-pretreated rats. ICAM-1 protein expression was significantly decreased in all pretreatment groups after OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging, interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE lungs. These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats.
authors.affiliation: Dept. of Occupational Therapy, I-Shou Univ., No. 8 E-Da Road, Jiau-Shu Tsuen, Yan-Chau Shiang, Kaohsiung County 824, Tainan City, Republic of China (Taiwan). pingchia@mail2000.com.tw
authors.forename: Ping-Chia
authors.initials: PC
authors.lastname: Li
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Chen
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.forename: Shao-Chieh
authors.initials: SC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002392:Catechin / Q000378:metabolism / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010578:Petroleum; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D015208:Smoke Inhalation Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013373:Substance P / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001549:Benzamides; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010578:Petroleum; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D012906:Smoke; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; C073839:SR 48968; D002392:Catechin; D001205:Ascorbic Acid; C066892:CP 96345