title: Nicotine-induced inflammatory decreasing effect on passive skin arthus reaction in paraventricular nucleus-lesioned wistar rats.
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.
authors.affiliation: Laboratory Animal Research Center, Nara Medical University, Kashihara, Nara, Japan. k-kubo@naramed-u.ac.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubo
authors.forename: Taizo
authors.initials: T
authors.lastname: Kita
authors.forename: Itaru
authors.initials: I
authors.lastname: Narushima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakatani
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D001183:Arthus Reaction / Q000188:drug therapy* / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D015735:Mifepristone; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D003513:Cycloheximide; D003345:Corticosterone