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Research ArticleArticle

ON THE MECHANISMS OF 14C-NICOTINE DISTRIBUTION IN RAT SUBMAXILLARY GLAND IN VITRO

JAMES W. PUTNEY JR. and JOSEPH F. BORZELLECA
Journal of Pharmacology and Experimental Therapeutics July 1971, 178 (1) 180-191;
JAMES W. PUTNEY JR.
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JOSEPH F. BORZELLECA
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Abstract

The uptake and efflux of nicotine (N methyl-14C) were studied under various incubation and washout conditions. The 60-minute 14C-nicotine space at an extracellular pH of 7.40 was 4.037 ± 0.255 (S.E.) ml/g. Elevation or depression of extracellular pH brought about a significant increase or decrease, respectively, in the 14C-nicotine space. In all cases, the intracellular/extracellular ratios were greater than those calculated from the intracellulax pH determined by 5,5-dimethyloxazolidine-2,4-dione-2-14C distribution. CN-, 10-5 M, or an increase (x 100) in the extracellular concentration of nicotine did not affect the 60-minute spaces. Temperature dependence of the 60-minute spaces was observed but could be explained solely by the effect of temperature on the pK6 of the drug. Increasing or decreasing pH during efflux significantly decreased and increased the observed rate constants. It is conduded that the uptake of 14C-nicotine by submaxillary glands occurs by passive diffusion of the un-ionized species across the cell membrane and is followed by binding to intracellular sites and/or partitioning of the un-ionized drug into lipid compartments. The rate-limiting step in efflux is the dissociation of the drug from the cell membrane. The dissociation is greatly facilitated by the collision of a proton from the extracellular hydrogen ion pool.

Footnotes

    • Received January 21, 1971.
    • Accepted April 2, 1971.
  • © 1971, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 178, Issue 1
1 Jul 1971
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Research ArticleArticle

ON THE MECHANISMS OF 14C-NICOTINE DISTRIBUTION IN RAT SUBMAXILLARY GLAND IN VITRO

JAMES W. PUTNEY and JOSEPH F. BORZELLECA
Journal of Pharmacology and Experimental Therapeutics July 1, 1971, 178 (1) 180-191;

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Research ArticleArticle

ON THE MECHANISMS OF 14C-NICOTINE DISTRIBUTION IN RAT SUBMAXILLARY GLAND IN VITRO

JAMES W. PUTNEY and JOSEPH F. BORZELLECA
Journal of Pharmacology and Experimental Therapeutics July 1, 1971, 178 (1) 180-191;
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