Acceleration of noradrenaline biosynthesis in the guinea‐pig vas deferens by potassium

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Abstract
1 . Increasing the concentration of KC1 in Krebs-Henseleit bicarbonate solution enhanced the formation of 14C-noradrenaline (14C-NA) from 14C-tyrosine in the guinea-pig vas deferens. In 52 mm KC1 Krebs-Henseleit solution the specific activity of the newly formed 14C-NA was double that of controls. 2 . The rate of synthesis of 14C-NA from 14C-tyrosine was constant for up to 2 h in 52 mm KC1 Krebs-Henseleit solution and for 4 h in unmodified Krebs-Henseleit solution. 3 . There was no increase in NA formation in the presence of KC1 rich Krebs-Henseleit solution if 14C-DOPA was used as the starting substrate instead of 14C-tyrosine. 4 . The specific activity of 14C-tyrosine in the high KC1 treated vas deferens was 80% of that of control tissues. Thus the enhanced synthesis of 14C-NA in high KC1 Krebs-Henseleit solution did not arise from an increase in the specific activity of precursor. 5 . The effect of K+ on NA synthesis was not mimicked by ganglionic stimulants nor blocked by tetrodotoxin. 6 . Removal of Ca2+ ions or increasing the concentration of Mg2+ ions abolished the increase in synthesis of NA seen in high KC1 Krebs-Henseleit solution but left the basal rate of NA synthesis in unmodified Krebs-Henseleit solution unaltered. 7 . The spontaneous release of newly synthesized catecholamines (14C-labelled) or tritiated noradrenaline (3H-NA) from vasa deferentia was increased in 52 mm KC1 Krebs-Henseleit solution. Removal of Ca2+ ions reduced the increased efflux of newly synthesized amine in high KC1 media to that seen in unmodified Krebs-Henseleit solution. The efflux of 3H-NA was reduced to one-third of its former rate in the absence of Ca2+. 8 . High KC1 Krebs-Henseleit solution caused a substantial contraction of the vas deferens which was not abolished by tetrodotoxin. Release of 3H-NA paralleled the contractile response, and was likewise unaffected by tetrodotoxin. 9 . No evidence was obtained for any alterations in the activity of tyrosine hydroxylase, the rate limiting enzyme in the formation of NA from tyrosine, in homogenates of vas deferens which had been treated with 52 mm KC1 Krebs-Henseleit solution. 10 . These results support the hypothesis that acceleration of NA synthesis occurs when tyrosine hydroxylase is freed from end-product inhibition by the release of noradrenaline, brought about in this case, by high concentrations of KC1.