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Title: Nicotine-induced inflammatory decreasing effect on passive skin arthus reaction in paraventricular nucleus-lesioned wistar rats. Author: Kubo K, Kita T, Narushima I, Tanaka T, Nakatani T, Nakashima T. Journal: Pharmacol Toxicol; 2003 Mar; 92(3):125-30. PubMed ID: 12753427. Abstract: To evaluate the relationship between nicotine and immunological inflammation, we investigated the effects of nicotine on plasma extravasation of the passive skin Arthus reaction, elicited 4 hr after sensitizing skin with antiserum, and serum corticosterone levels in rats. Pretreatment with a single subcutaneous injection of nicotine (0.4 or 0.8 mg/kg) 30 or 60 min. before antigen challenge attenuated the passive skin Arthus reaction immunological inflammation. Serum corticosterone levels were dose-dependently increased 30 and 60 min. after nicotine administration. Both markers co-varied with a similar dose-response and time course after the nicotine-treatment. In addition, we also examined these nicotine-induced responses after bilateral lesions of the hypothalamic paraventricular nucleus; both the nicotine-induced suppression of immunological inflammation and the increased serum corticosterone levels were attenuated in bilateral paraventricular nucleus-lesioned animals. Moreover, the immunological inflammatory decreasing effects of a single subcutaneous injection of nicotine (0.4 mg/kg) were antagonized by intraperitoneal preinjection with mecamylamine (1.0 mg/kg; blocking the brain nicotinic acetylcholine receptors) as well as by subcutaneous preinjection with mifepristone (30 mg/kg; a glucocorticoid receptor antagonist) but not by intraperitoneal preinjection with hexamethonium (2.0 mg/kg; a peripheral nicotinic acetylcholine receptors antagonist). Finally, intraperitoneal preinjection with cycloheximide (2 mg/kg), a protein synthesis inhibitor, abolished both the inhibitory effect of nicotine (0.4 mg/kg) on the dye leakage and the elevation of blood corticosterone levels. These findings indicate that the nicotine-induced decreasing effect on immunological inflammatory response may be related to serum corticosterone levels elevated by an activation of the paraventricular nucleus through the brain nicotinic acetylcholine receptors.[Abstract] [Full Text] [Related] [New Search]