Modulation of the actions of tyrosine by alpha 2-adrenoceptor blockade

1. Eight normal subjects were given, in double-blind, random order L-tyrosine 50, 250 and 500 mg kg-1 and placebo orally. Plasma tyrosine concentrations rose in a dose-dependent manner, without affecting the concentrations of the other large neutral amino acids. Tyrosine stimulated the secretion of prolactin and thyrotrophin (TSH) but had no effect on the plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone or the gonadotrophins. 2. The lack of a stimulant effect of tyrosine on ACTH secretion was presumed to be due to activation of one of the negative feedback mechanisms that control the rate of synthesis and release of the catecholamines, and this hypothesis was tested by examining the effects of the alpha 2-adrenoceptor antagonist idazoxan on the actions of tyrosine. 3. Seven normal males were given on 6 separate occasions tyrosine 250 and 500 mg kg-1 and placebo orally following pretreatment with saline and idazoxan (0.1 mg kg-1 i.v.). Following pretreatment with idazoxan, tyrosine stimulated the secretion of ACTH and noradrenaline in a dose-dependent manner, although neither tyrosine nor idazoxan on their own had any effect on the secretion of either substance. 4. The lack of effect of tyrosine when given on its own appears to be due, to partly, to activation of alpha 2-adrenoceptors, which inhibit the release of noradrenaline. Idazoxan caused a small increase in systolic blood pressure, both when given on its own and in combination with tyrosine. Neither tyrosine nor idazoxan had any significant effect on the state of behavioural arousal, as measured by visual analogue scales, or on the secretion of growth hormone or the gonadotrophins.