Thromboxane agonist (U46619) potentiates norepinephrine efflux from adrenergic nerves.
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.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013931:Thromboxanes / Q000494:pharmacology; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D014316:Tritium; D000804:Angiotensin II; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D009638:Norepinephrine