Thromboxane mimetics enhance adrenergic neurotransmission in the rabbit-isolated portal vein.
The thromboxane/prostaglandin H mimetics, U46619 and carbocyclic thromboxane A2 (cTA2) were examined for influences on adrenergic neural responses. Force generation in response to low-frequency electrical stimulation was enhanced 21 +/- 5% by U46619 and 20 +/- 4% by cTA2. These effects were antagonized by the thromboxane/prostaglandin H receptor antagonist, SQ29548. Norepinephrine-induced contractions were not significantly potentiated by the presence of U46619 or cTA2. Norepinephrine release from electrically stimulated portal veins was augmented by U46619 as compared to control preparations (p less than 0.05). These results are consistent with the hypothesis that thromboxane/prostaglandin H receptors mediate a potentiation of adrenergic neural responses by augmenting the release of neurotransmitters from adrenergic nerves and are inconsistent with a postjunctional potentiative site of action. The constrictor effect of U46619 on portal vein smooth muscle was less potent than the potentiative effect on neural responses suggesting that the latter would be a more likely physiological action of thromboxanes or prostaglandin endoperoxides in this vascular bed.
Stein
E A
EA
Department of Pharmacology, University of Minnesota-Duluth School of Medicine, MN 55812.
Trachte
G J
GJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004558:Electric Stimulation; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000294:innervation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D009638:Norepinephrine