JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by LANGER, S. Z.
Right arrow Articles by TRENDELENBURG, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by LANGER, S. Z.
Right arrow Articles by TRENDELENBURG, U.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ATROPINE
*COCAINE
*PHENTOLAMINE
*RESERPINE
Journal of Pharmacology And Experimental Therapeutics, Vol. 167, Issue 1, 117-142, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

THE EFFECT OF A SATURABLE UPTAKE MECHANISM ON THE SLOPES OF DOSE-RESPONSE CURVES FOR SYMPATHOMIMETIC AMINES AND ON THE SHIFTS OF DOSE-RESPONSE CURVES PRODUCED BY A COMPETITIVE ANTAGONIST

S. Z. LANGER 1 and U. TRENDELENBURG 1

1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Experiments with normal nictitating membranes of pithed cats as well as with isolated normal nictitating membranes show that dose-response curves for a variety of sympathomimetic amines are not parallel: slopes of dose-response curves are inversely related to potency of the amines. The same relationship was observed for a given amine when potency was changed experimentally by decentralization (increase in potency) or by phentolamine (decrease in potency). Since this relationship was not observed after either denervation or cocaine, the phenomenon appears to be related to the uptake of sympathomimetic amines by adrenergic nerve endings. A model is proposed to demonstrate the influence of saturation of uptake on the concentration of amines at the receptors of the effector organ. From the model several postulates were made and tested experimentally. The results indicate that saturation of uptake is one of the factors influencing slopes of dose-response curves. Moreover, saturation of uptake influences the magnitude of shifts of dose-response curves to the left (after decentralization) or to the right (after phentolamine). As a result, a competitive antagonist (phentolamine) appears to be less effective in antagonizing l-norepinephrine on the normal than on the denervated nictitating membrane. For an agent which does not seem to be taken up (i.e., acetylcholine), there is equal antagonism by a competitive antagonist (i.e., atropine) in normal and denervated nictitating membranes.

Submitted on August 12, 1968
Accepted on October 28, 1968




This article has been cited by other articles:


Home page
 J. Physiol.Home page
M. Yeoh, E. M McLachlan, and J. A Brock
Chronic decentralization potentiates neurovascular transmission in the isolated rat tail artery, mimicking the effects of spinal transection
J. Physiol., December 1, 2004; 561(2): 583 - 596.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics.