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Developmental effects of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, on growth and on levels and turnover of catecholamines.

Publication ,  Journal Article
Slotkin, TA; Bartolome, J; Whitmore, WL
Published in: Life Sci
November 21, 1983

To examine the potential participation of histamine in cellular development, neonatal rats were given daily 50 mg/kg doses of alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of histidine decarboxylase; previous studies have shown this regimen to deplete both neurotransmitter and nonneurotransmitter pools of histamine. No inhibition of growth was observed for either body weight, brain weight, heart weight or kidney weight; indeed, kidney weights tended to become supranormal toward weaning in the FMH-treated pups. Similarly, FMH failed to affect protein synthesis, confirming the lack of systemic toxicity of this amino acid as well as indicating that maintenance of histamine levels is not required for growth to proceed. In contrast, FMH did have a deleterious effect on development of the cardiac-sympathetic axis, with deficits in norepinephrine levels appearing during the third postnatal week. The deficits were not present in other catecholaminergic systems (brain noradrenergic or dopaminergic neurons and renal sympathetic neurons). The subnormal cardiac norepinephrine levels were preceded by a sharp increase in the turnover of norepinephrine at precisely the age at which central control of sympathetic tone first appears. The developmental effects of FMH indicate that, although it is unlikely that histamine participates in a major way in general control of cellular maturation, a more selective role for histamine as a trophic agent or neurotransmitter may exist during defined periods in nervous system development.

Duke Scholars

Published In

Life Sci

DOI

ISSN

0024-3205

Publication Date

November 21, 1983

Volume

33

Issue

21

Start / End Page

2137 / 2145

Location

Netherlands

Related Subject Headings

  • Sympathetic Nervous System
  • Rats, Inbred Strains
  • Rats
  • Pharmacology & Pharmacy
  • Norepinephrine
  • Myocardium
  • Methylhistidines
  • Kidney
  • Histidine Decarboxylase
  • Histidine
 

Citation

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Slotkin, T. A., Bartolome, J., & Whitmore, W. L. (1983). Developmental effects of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, on growth and on levels and turnover of catecholamines. Life Sci, 33(21), 2137–2145. https://doi.org/10.1016/0024-3205(83)90338-7
Slotkin, T. A., J. Bartolome, and W. L. Whitmore. “Developmental effects of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, on growth and on levels and turnover of catecholamines.Life Sci 33, no. 21 (November 21, 1983): 2137–45. https://doi.org/10.1016/0024-3205(83)90338-7.
Slotkin, T. A., et al. “Developmental effects of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, on growth and on levels and turnover of catecholamines.Life Sci, vol. 33, no. 21, Nov. 1983, pp. 2137–45. Pubmed, doi:10.1016/0024-3205(83)90338-7.
Journal cover image

Published In

Life Sci

DOI

ISSN

0024-3205

Publication Date

November 21, 1983

Volume

33

Issue

21

Start / End Page

2137 / 2145

Location

Netherlands

Related Subject Headings

  • Sympathetic Nervous System
  • Rats, Inbred Strains
  • Rats
  • Pharmacology & Pharmacy
  • Norepinephrine
  • Myocardium
  • Methylhistidines
  • Kidney
  • Histidine Decarboxylase
  • Histidine