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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 16, 2003; DOI: 10.1124/jpet.103.052233

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Received for publication March 31, 2003.
Revised April 15, 2003.
Accepted for publication May 8, 2003.

Effect of Reboxetine on Sympathetic Neuroeffector Transmission in Rabbit Carotid Artery

Lasse E. Rasmussen 1 Ove A. Nedergaard 1*

1 University of Southern Denmark

* Address correspondence to: E-mail: oanedergaard{at}health.sdu.dk

Abstract

The effect of reboxetine on sympathetic neuroeffector transmission in rabbit isolated carotid artery was examined. Reboxetine (10-8 - 3 x 10- 6 M), and cocaine (10-6 - 3 x 10- 5 M), but not desipramine (10-8 - 3 x 10-7 M), increased contractions evoked by electrical field stimulation. At higher concentrations, reboxetine (10-4 M), cocaine (3 x 10- 4 M) and desipramine (3 x 10-7 - 10- 5 M) inhibited the neurogenic contractions. The enhancement seen with reboxetine and cocaine was partially reversible, while the inhibition was readily reversible. Reboxetine (10-7 M) and cocaine (10-5 M) prevented the inhibitory action of bretylium (10-6 M). Reboxetine (10- 8 - 10-5 M), desipramine (10- 7 - 10-4 M) and cocaine (10- 6 - 10-5 M) increased the stimulation- evoked [3H]norepineprine release. Pargyline (5 x 10-4 M) augmented the facilitatory effect of reboxetine (3 x 10-9 - 10-6 M) and cocaine (10-7 - 3 x 10-5 M). Reboxetine (10-8 - 10-6 M), desipramine (10-8 - 10-6 M) and cocaine (3 x 10-8 - 10-5 M) reduced the [3H]norepinephrine (10-8 M) uptake. Reboxetine (10-7 M) and cocaine (10-5 - 2 x 10-4 M) enhanced the contractions evoked by phenylephrine and norepinephrine. Higher concentrations of reboxetine antagonized the contractions. Reboxetine (10-5 - 6 x 10- 5 M) antagonized the contractions evoked by potassium. The contractions evoked by tyramine (3 x 10-6 - 10-3 M) was reduced by reboxetine (3 x 10-8 - 10-6 M) and by cocaine (10-7 - 10-5 M). We conclude that reboxetine inhibits the membrane amine pump (uptake-1) in the terminals of postganglionic adrenergic neurons in a cocaine-like manner.


Key words: Adrenergic neurons, Carotid artery, Cocaine, Norepinephrine release, Norepinephrine uptake inhibitor, Reboxetine


This article has been cited by other articles:


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 Am. J. Physiol. Heart Circ. Physiol.Home page
L. E. Rasmussen, P. M. Vanhoutte, B. L. Jensen, and O. Skott
Continuous flow augments reactivity of rabbit carotid artery by reducing bioavailability of NO despite an increase in release of EDHF
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1521 - H1528.
[Abstract] [Full Text] [PDF]


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