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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

The Effects of Cocaine and Nicotine on Amino Acid Transport across the Human Placental Cotyledon Perfused In Vitro

Aleksandra Pastrakuljic, Lidia O. Derewlany, Brenda Knie and Gideon Koren
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 141-146;
Aleksandra Pastrakuljic
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Lidia O. Derewlany
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Brenda Knie
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Gideon Koren
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Abstract

The inhibitory effects of cocaine and nicotine on placental amino acid transport, as a mechanism contributing to intrauterine growth restriction, were investigated in the in vitro placental perfusion model. Amino acids that represent substrates for known placental transporters were selected: alanine (system A), glutamine (system N), phenylalanine and valine (system l), and arginine (system y+). Amino acid accumulation on the fetal side was measured in the absence of cocaine or nicotine (n = 7) and in the presence of 1.2 μg/ml cocaine (n = 6), 120 ng/ml nicotine (n = 6), or both (n = 6). Neither cocaine nor nicotine alone significantly inhibited alanine transport, whereas their combination did (P = .02). Significant inhibition of arginine transport was detected with nicotine (P = .007), cocaine (P = .01), and their combination (P = .01), whereas phenylalanine (P = .03, P = .04) and valine (P = .03, P = .04) transport was affected by cocaine and the combination of cocaine and nicotine, respectively. For glutamine, neither cocaine, nicotine, nor their combination had a statistically significant inhibitory effect. In conclusion, both cocaine and nicotine may contribute to fetal growth restriction by interfering with the activity of amino acids transporters that are necessary to maintain the nutrient gradients associated with normal fetal growth.

Footnotes

  • Send reprint requests to: Dr. Gideon Koren, Department of Clinical Pharmacology (rm. 8239), Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8. E-mail:placgrp{at}sickkids.on.ca

  • ↵1 This work was supported by a grant from the Medical Research Council of Canada.

  • Abbreviations:
    IUGR
    intrauterine growth restriction
    F/M
    fetal/maternal
    RIA
    radioimmunoassay
    hCG
    human chorionic gonadotrophin
    HBSS
    Hanks' balanced salt solution
    • Received January 5, 2000.
    • Accepted March 17, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 2000
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

The Effects of Cocaine and Nicotine on Amino Acid Transport across the Human Placental Cotyledon Perfused In Vitro

Aleksandra Pastrakuljic, Lidia O. Derewlany, Brenda Knie and Gideon Koren
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 141-146;

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

The Effects of Cocaine and Nicotine on Amino Acid Transport across the Human Placental Cotyledon Perfused In Vitro

Aleksandra Pastrakuljic, Lidia O. Derewlany, Brenda Knie and Gideon Koren
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 141-146;
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