Effects of the beta 2-adrenoceptor agonist clenbuterol on tyrosine and tryptophan in plasma and brain of the rat.
The beta 2-adrenoceptor agonist, clenbuterol (initially 5 mg/kg), was found to significantly reduce plasma tyrosine and raise brain tryptophan levels (P less than 0.01). By comparison, decreases in plasma tryptophan and increases in brain tyrosine were small and often nonsignificant. Amino acid levels measured in different brain regions revealed that the elevations were similar among the cerebellum, striatum, and cortex. These effects were partially blocked by propanolol but not by atenolol. The ED50 was estimated from dose-response curves to be about 0.05 mg/kg for both the decrease in plasma tyrosine and the increase in brain tryptophan. The effects of low doses of clenbuterol were prevented completely by propranolol. Peripheral organs displayed strikingly different patterns of change in amino acid concentrations. Only the spleen had any accumulation of tryptophan, but that was much less than in brain. In contrast, tyrosine and tryptophan were decreased in heart and unaltered in liver; tyrosine was decreased in lung. The elevation in brain tryptophan levels was attenuated by the beta 2-antagonist, ICI 118,551, but not by the beta 1-antagonist, betaxolol; but the reduction in plasma tyrosine was unaffected by either drug. The serotonin antagonist, methysergide, failed to block the effects of clenbuterol. We conclude that changes in amino acid concentrations produced by clenbuterol are mediated by beta 2-adrenoceptor stimulation. Although the increases in brain tyrosine and tryptophan were similar to increases in the plasma ratios of these amino acids to the sum of the other large neutral amino acids competing for transport into the brain, the disparity between the effects of ICI 118,551 in brain and plasma suggests that clenbuterol may also have a direct action in brain to regulate levels of aromatic amino acids. Since clenbuterol has been purported to have an antidepressant effect and since other antidepressants also increase brain tryptophan, this may be a common feature of antidepressant drug action.
Edwards
D J
DJ
Department of Pharmacology-Physiology, University of Pittsburgh School of Dental Medicine, PA 15261.
Sorisio
D A
DA
Knopf
S
S
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D015784:Betaxolol; D001923:Brain Chemistry / Q000187:drug effects*; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014364:Tryptophan / Q000032:analysis* / Q000097:blood; D014443:Tyrosine / Q000032:analysis* / Q000097:blood
D000596:Amino Acids; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014443:Tyrosine; C026777:ICI 118551; D014364:Tryptophan; D011433:Propranolol; D015784:Betaxolol; D002976:Clenbuterol; D008784:Methysergide