Ethanol-induced changes in tyrosine hydroxylase activity in adrenal glands of mice selectively bred for differences in sensitivity to ethanol

TA French, JM Masserano and N Weiner

In the present study catecholaminergic systems in the adrenal glands of mice selectively bred for differences in sensitivity to ethanol, the long-sleep (LS) and short-sleep (SS) mice, have been examined. Tyrosine hydroxylase (TH) activity and catecholamine levels were measured in the adrenal glands at various times after a single injection of ethanol (4.0 g/kg i.p.). Basal levels of TH activity, epinephrine and norepinephrine are significantly higher in the adrenal glands of LS mice by 87, 20, and 26%, respectively. Ten minutes after ethanol administration, LS mouse adrenal gland TH activity is decreased by 33% whereas SS mouse adrenal gland TH activity is increased by 68%. At 25 and 125 min after ethanol, SS mouse adrenal gland TH activity is no longer increased, but the decrease in TH activity persists in adrenals of LS mice. The corresponding adrenal gland catecholamine levels are unchanged in the LS and SS mice at all times measured except at 125 min in LS mice when both epinephrine (24%) and norepinephrine (31%) are decreased. The increase in SS adrenal gland TH activity at 10 min after ethanol administration is associated with an increase in the affinity of the enzyme for the pterin cofactor (decreased Km). Conversely, the decrease in TH activity at 10 min after ethanol in LS mice is associated with an increase in Km for the pterin cofactor. The Vmax is unchanged by ethanol treatment in either line. Prior administration of chlorisondamine (15 mg/kg i.p.) has no effect on either the ethanol- induced changes in adrenal gland TH activity at 10 min or the sleep time of LS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 232, Issue 2, pp. 315-321, 02/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics