Drugs altering insulin secretion: effects on plasma and brain concentrations of aromatic amino acids and on brain 5-hydroxytryptamine turnover.

Abstract

1 An investigation was made into the effects of drugs which alter insulin secretion on the concentrations of tryptophan and other aromatic amino acids in plasma and brain and on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brain. Drugs used were streptozotocin, propranolol, tolbutamide and phentolamine. 2 Tolbutamide and phentolamine increased the plasma insulin concentrations by 100% and 300% respectively but with little effect on the brain/plasma ratios for the aromatic amino acids. Previously propranolol was found to decrease plasma insulin by 50% without altering the above ratios. The ratios were decreased by streptozotocin but only when plasma insulin fell by more than 50%. 3 Phentolamine and propranolol did not alter the brain/plasma ratios for the aromatic amino acids in streptozotocin-treated rats. 4 The results suggest that only large changes of insulin secretion e.g. those associated with food intake or aminophylline injection are likely to alter appreciably the brain/plasma ratios for the aromatic amino acids. 5 Tolbutamide displaced tryptophan from its binding to plasma albumin and increased brain 5-HIAA probably by inhibiting 5-HIAA efflux from brain. The other drugs did not alter brain 5-HT or 5-HIAA concentrations.