PT  - JOURNAL ARTICLE
AU  - W J Wu
AU  - S B Pruett
TI  - Suppression of splenic natural killer cell activity in a mouse model for binge drinking. II. Role of the neuroendocrine system.
DP  - 1996 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1331--1339
VI  - 278
IP  - 3
4099  - http://jpet.aspetjournals.org/content/278/3/1331.short
4100  - http://jpet.aspetjournals.org/content/278/3/1331.full
SO  - J Pharmacol Exp Ther1996 Sep 01; 278
AB  - Ethanol (EtOH) suppresses natural killer (NK) cell activity in the spleen in a binge drinking model in mice. Direct effects of EtOH and its metabolites are not the major cause of this suppression. In this study, the role of catecholamines, glucocorticoids and opioids in EtOH-induced suppression of NK cell activity in mice was evaluated. In addition, the role of GABA-A receptors was examined. The catecholamine antagonists phentolamine, nadolol and propranolol (delivered by a timed-release pellet) respectively exacerbated, partially blocked and had no effect on EtOH-induced suppression of NK cell activity. Chemical sympathectomy significantly reduced the suppression of NK cell activity by EtOH. The glucocorticoid antagonist RU 486 (mifepristone) did not affect EtOH-induced suppression of NK cell activity, and exogenous corticosterone only marginally suppressed NK cell activity. The opioid antagonist naltrexone (delivered by a timed-release pellet) did not block suppression of NK cell activity by EtOH. Thus glucocorticoids and opioids are not the major causes of EtOH-induced suppression of NK cell activity, and catecholamines seem only partially responsible for this effect. Involvement of GABA-A receptors was suggested by the ability of Ro15-4513 to decrease EtOH-induced NK suppression. Other agents were less effective, which suggested a possible role for the diazepam-insensitive GABA-A sites that are recognized by Ro15-4513. The failure of diazepam to suppress NK activity also suggests that increased chloride flux through diazepam-sensitive GABA-A receptors (which is caused by EtOH as well as diazepam) does not mediate NK suppression in this model.