Thromboxane agonist (U46619) potentiates norepinephrine efflux from adrenergic nerves

GJ Trachte

The effect of the synthetic thromboxane/prostaglandin (PG) H2 agonist U46619 on the electrically stimulated rabbit isolated was deferens was examined to test for thromboxane influences on adrenergic nerves. U46619 effects on force generation, [3H] norepinephrine release and norepinephrine-induced contractions were assessed to determine the mechanism of action. U46619 maximally enhanced adrenergic force generation 135 +/- 24% at a concentration of 100 nM. U46619 potentiated maximal contractile effects of exogenously administered norepinephrine 16 +/- 4% and augmented [3H]norepinephrine release from electrically stimulated preparations 142 +/- 44%. A competitive thromboxane/PGH2 receptor antagonist, SQ29548, significantly shifted the concentration- response curve for U46619 to the right in a concentration-dependent manner and blocked U46619-induced tritium release. Thus, U46619 appears to potentiate neurotransmitter release by interacting with thromboxane/PGH2 receptors. Because SQ29548 did not prevent the potentiation of norepinephrine contractions by U46619, the postjunctional effect may be independent of thromboxane/PGH2 receptors. We interpret these results to be indicative of both pre- and postjunctional sites of action of U46619. The physiological importance of these thromboxane effects is unknown currently.

Volume 237, Issue 2, pp. 473-477, 05/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				M. J. Wacker, S. R. Best, L. M. Kosloski, C. J. Stachura, R. L. Smoot, C. B. Porter, and J. A. Orr Thromboxane A2-induced arrhythmias in the anesthetized rabbit Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1353 - H1361. [Abstract] [Full Text] [PDF]