The effect of 6-aminonicotinamide blockade of the pentose phosphate pathway on catecholamines in the rat adrenal medulla, superior cervical ganglion, hypothalamus and synaptosome fractions.

The effect on tissue catecholamines of blockade of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) was studied in the rat. 6-AN at 35-50 mg kg-1 persistently lowered the adrenaline content in the adrenal gland to less than 10% of control values and caused a 50% loss of noradrenaline, which recovered. When the amine turnover rate was increased by a preceding period of drum stress, 6-AN also consistently depressed noradrenaline in the gland. 6-AN was without significant effect on the noradrenaline concentration in heart tissue, hypothalamus and superior cervical ganglion and did not affect the uptake or release of catecholamines in vitro. The possibility is discussed that 6-AN interferes with the biosynthesis of catecholamines, when it blocks the pentose phosphate pathway, by decreasing the supply of reducing equivalents in the form of NADPH which are necessary for the tetrahydropteridine cofactors of tyrosine hydroxylase.