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. 1972 Dec;46(4):696–707. doi: 10.1111/j.1476-5381.1972.tb06894.x

Effect of drugs on the synthesis of noradrenaline in guinea-pig vas deferens

Margaret C Boadle-Biber, R H Roth
PMCID: PMC1666369  PMID: 4655268

Abstract

1. Reserpine in vitro (10-5M) caused a profound inhibition (>85%) of the formation of both 14C-catecholamine (14C-CA) and 14C-dihydroxyphenylalanine (14C-DOPA) (in the presence of the amino acid decarboxylase inhibitor brocresine) from 14C-tyrosine in guinea-pig vas deferens. The magnitude of the inhibition was similar for both 14C-CA and 14C-DOPA suggesting that the inhibition occurred primarily at the tyrosine hydroxylase step.

2. One hour after in vivo treatment with reserpine (1 mg/kg) when tissue stores of noradrenaline (NA) were depleted by 50%, there was a significant inhibition of the formation of 14C-DOPA. Twenty-four hours after such treatment, when endogenous NA could no longer be detected, synthesis of 14C-DOPA was indistinguishable from untreated controls. However a 45% inhibition of 14C-DOPA synthesis from 14C-tyrosine could be produced in tissues which had been depleted of NA for 24 h or 48 h by the addition of reserpine, 10-5M, to the incubation medium.

3. Addition of pteridine cofactor, 2-amino-6,7,-dimethyl-4-hydroxy-5,6,7,8-tetrahydropteridine, to the incubation medium in a concentration of 5 × 10-3M enhanced the formation of both 14C-CA and 14C-DOPA from 14C-tyrosine in guinea-pig vas deferens. In 52 mM KCl Krebs-Henseleit medium 14C-CA formation increased from 2·58±0·20 (nmol/g)/h to 6·35±0·47 (nmol/g)/h whilst 14C-DOPA formation increased from 5·04±0·88 (nmol/g)/h to 11·29±0·59 (nmol/g)/h.

4. Pteridine cofactor (5 × 10-3M) did not reverse the inhibition of 14C-DOPA formation seen with reserpine (10-5M) in previously untreated tissues or in vasa deferentia from animals pretreated with reserpine 1 mg/kg for 24 hours. However, the inhibition did disappear in the presence of pteridine cofactor when treatment with reserpine was prolonged to 48 h and included two doses of reserpine of 2 mg/kg.

5. Tyramine (5·8 × 10-5M) and bretylium (10-5M) in vitro inhibited the formation of 14C-CA and 14C-DOPA from 14C-tyrosine to the same extent in guinea-pig vas deferens again indicating that their major site of action is on tyrosine hydroxylase. The inhibitory effects were reversed by pteridine cofactor.

6. Synthesis of 14C-NA from 14C-tyrosine in calf splenic nerve was not increased by incubating the tissue in 52 mM KCl-Krebs-Henseleit solution.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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