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Acceleration of noradrenaline biosynthesis in the guinea‐pig vas deferens by potassium
Author(s) -
BOADLEBIBER MARGARET C.,
HUGHES J.,
ROTH R. H.
Publication year - 1970
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1970.tb10648.x
Subject(s) - vas deferens , chemistry , bicarbonate , sodium , tyrosine , medicine , biochemistry , endocrinology , organic chemistry
Summary1 . Increasing the concentration of KC1 in Krebs‐Henseleit bicarbonate solution enhanced the formation of 14 C‐noradrenaline ( 14 C‐NA) from 14 C‐tyrosine in the guinea‐pig vas deferens. In 52 m m KC1 Krebs‐Henseleit solution the specific activity of the newly formed 14 C‐NA was double that of controls. 2 . The rate of synthesis of 14 C‐NA from 14 C‐tyrosine was constant for up to 2 h in 52 m m 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 14 C‐DOPA was used as the starting substrate instead of 14 C‐tyrosine. 4 . The specific activity of 14 C‐tyrosine in the high KC1 treated vas deferens was 80% of that of control tissues. Thus the enhanced synthesis of 14 C‐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 Ca 2+ ions or increasing the concentration of Mg 2+ 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 ( 14 C‐labelled) or tritiated noradrenaline ( 3 H‐NA) from vasa deferentia was increased in 52 m m KC1 Krebs‐Henseleit solution. Removal of Ca 2+ ions reduced the increased efflux of newly synthesized amine in high KC1 media to that seen in unmodified Krebs‐Henseleit solution. The efflux of 3 H‐NA was reduced to one‐third of its former rate in the absence of Ca 2+ . 8 . High KC1 Krebs‐Henseleit solution caused a substantial contraction of the vas deferens which was not abolished by tetrodotoxin. Release of 3 H‐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 m m 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.