title: Adrenal medullary modulation of the inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine.
abstract: In the present experiments, we studied the effect of i.t. nicotine on synovial bradykinin-induced plasma extravasation (BK-PE), assessed by measurement of extravasation of Evan's blue dye into the rat knee joint. We report that in normal rats, i.t. nicotine dose-dependently inhibited BK-PE; the dose required was 100 times greater than the effective s.c. dose. In adrenal medullectomized rats, i.t. nicotine inhibited BK-PE at doses 10(6) times smaller than in rats with intact adrenal medullae. A similar leftward shift in the i.t. nicotine dose-response curve was seen in normal rats after blocking peripheral nicotinic receptors by hexamethonium or after bilateral denervation of the adrenal medulla. Intra-articular infusion of the knee joint in normal rats with knee joint perfusate collected from donor rats that had received i.t. nicotine decreased BK-PE significantly. Denervation of the sciatic nerves in the donor rat did not affect this action of i.t. nicotine. Perfusate collected from adrenal medullectomized donor rats that had received i.t. nicotine resulted in a greater decrease of BK-PE compared to the decrease produced by perfusate from normal donor rats that received i.t. nicotine. Intra-articular pretreatment of recipient rats with different receptor antagonists [phentolamine (alpha adrenoceptors), ICI-118,551 (beta 2 adrenoceptors), methysergide (serotoninergic S1/2 receptors) or naloxone (opioid receptors)] did not affect the BK-PE response produced by this perfusate. Nicotine, when administered i.t., can inhibit synovial BK-PE, but this effect is expressed only at high doses in the presence of an intact adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of California, School of Medicine, San Francisco.
authors.forename: F J
authors.initials: FJ
authors.lastname: Miao
authors.forename: M F
authors.initials: MF
authors.lastname: Dallman
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: A I
authors.initials: AI
authors.lastname: Basbaum
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007278:Injections, Spinal; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D010949:Plasma / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
chemical_list: D006584:Hexamethonium Compounds; D011412:Propanolamines; D011978:Receptors, Nicotinic; D018738:Hexamethonium; C026777:ICI 118551; D009538:Nicotine; D001920:Bradykinin