Adrenal medullary modulation of the inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine
Miao, F.J.; Dallman, M.F.; Benowitz, N.L.; Basbaum, A.I.; Levine, J.D.
Journal of Pharmacology and Experimental Therapeutics 264(2): 839-844
1993
ISSN/ISBN: 0022-3565 PMID: 8094755 Document Number: 419261
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 S-1/2 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. This effect of i.t. nicotine appears to be mediated, at least in part, by a transferable (probably circulating) substance(s) that can be detected by cross-perfusion experiments.