JPET xPharm- The Comprehensive Pharmacology Reference

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 Porter, C. C.
Right arrow Articles by Stone, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Porter, C. C.
Right arrow Articles by Stone, C. A.
Journal of Pharmacology And Experimental Therapeutics, Vol. 140, Issue 3, 308-316, 1963
Copyright © 1963 by American Society for Pharmacology and Experimental Therapeutics

EFFECT OF 6-HYDROXYDOPAMINE AND SOME OTHER COMPOUNDS ON THE CONCENTRATION OF NOREPINEPHRINE IN THE HEARTS OF MICE

Curt C. Porter 1, James A. Totaro 1, and Clement A. Stone 1

1 Merck Institute for Therapeutic Research, West Point, Pennsylvania

Some compounds were examined for potency in depleting mouse heart norepinephrine, which was measured 16 hours (or 1 hour for tyramine) after intraperitoneal drug administration. These compounds, in order of increasing ED50's (dose, in mg/kg, required to half deplete heart norepinephrine) were: reserpine, metaraminol, 6-hydroxydopamine (2,4,5-trihydroxyphenethylamine), guanethidine and tyramine.

After administration of equipotent doses of the compounds, heart norepinephrine returned to normal with widely varying rates. Most rapid repletion occurred after tyramine, followed in order by guanethidine, metaraminol, reserpine and 6-hydroxydopamine.

Tyramine, administered 1 hour previously, blocked the longer-lasting depletion of heart norepinephrine by 6-hydroxydopamine, but not by metaraminol, guanethidine and reserpine. Under similar conditions, guanethidine blocked 6-hydroxydopamine and reserpine, but not metaraminol; and metaraminol blocked 6-hydroxydopamine.

A second suboptimal dose of reserpine, guanethidine or metaraminol, administered 1 day after a first dose, produced additional depletion of heart norepinephrine. However, a second dose of 6-hydroxydopamine produced no additional effect unless it was larger than the first dose. Consecutive dosing, at a 1-day interval, with reserpine, guanethidine and 6-hydroxydopamine, in any combination of two in either sequence, produced additive depletion of heart norepinephrine.

The data can be interpreted, within the framework of the two-pool concept of norepinephrine storage, as follows:

1. Reserpine releases norepinephrine by acting upon pool 1; guanethidine, like bretylium, blocks the action of reserpine on this pool, but does not itself release norepinephrine from pool 1.

2. Tyramine, guanethidine and metaraminol, in order of increasing affinity for norepinephrine binding sites, release the amine through pool 2.

3. 6-Hydroxydopamine, although possessing less affinity for binding sites of pool 2 than tyramine, metaraminol and guanethidine, destroys or alters the binding sites in such a way that they must be replaced.

Submitted on January 18, 1963
Accepted on March 8, 1963




This article has been cited by other articles:


Home page
 ScienceHome page
A. Sandrock Jr and W. Matthew
An in vitro neurite-promoting antigen functions in axonal regeneration in vivo
Science, September 25, 1987; 237(4822): 1605 - 1608.
[Abstract] [PDF]

Home page
 ScienceHome page
B. D. Berger, C. D. Wise, and L. Stein
Nerve Growth Factor: Enhanced Recovery of Feeding after Hypothalamic Damage
Science, May 4, 1973; 180(4085): 506 - 508.
[Abstract] [PDF]

Home page
 ScienceHome page
L. Stein and C. D. Wise
Possible Etiology of Schizophrenia: Progressive Damage to the Noradrenergic Reward System by 6-Hydroxydopamine
Science, March 12, 1971; 171(3975): 1032 - 1036.
[Abstract] [PDF]

Home page
 ScienceHome page
F. E. Bloom, S. Algeri, A. Groppetti, A. Revuelta, and E. Costa
Lesions of Central Norepinephrine Terminals with 6-OH-Dopamine: Biochemistry and Fine Structure
Science, December 5, 1969; 166(3910): 1284 - 1286.
[Abstract] [PDF]


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

Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics.