title: Interaction between alpha(1)- and alpha(2)-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries.
abstract: Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and alpha-adrenoceptor agonists. We tested the hypothesis that alpha(1)- and alpha(2)-adrenoceptors interact to enhance adrenergic reactivity of mesenteric veins. We studied neurogenic and agonist-induced constrictions of mesenteric veins and arteries in vitro. Norepinephrine concentration-response curves were left-shifted in veins compared to arteries. UK 14,304 (0.01-1 microM, alpha(2)-adrenoceptor receptor agonist) did not constrict arteries or veins but enhanced constrictions and Ca(2+) signals mediated by alpha(1)-adrenoceptor stimulation in veins. Yohimbine (alpha(2)-adrenoceptor receptor antagonist) and MK912 (alpha(2C)-adrenoceptor receptor antagonist), but not alpha(2A)- or alpha(2B)-adrenoceptor antagonists, produced rightward shifts in norepinephrine concentration-response curves in veins. Pharmacological studies revealed that alpha(1D)-adrenoceptors mediate venous constrictions. Norepinephrine responses in veins from alpha(2C)-adrenoceptor knock-out (KO) mice were not different from wild type veins. Yohimbine inhibited norepinephrine constrictions in alpha(2C)-adrenoceptor KO veins suggesting that there is upregulation of other alpha(2)-adrenoceptors in alpha(2C)-KO mice. These data indicate that alpha(1D)- and alpha(2C)-adrenoceptors interact in veins but not in arteries. This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific alpha(2)-adrenoceptor linked Ca(2+) and perhaps other signaling pathways account for enhanced venous adrenergic reactivity.
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic. alhc@medicon.cz
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sporkova
authors.forename: Alex
authors.initials: A
authors.lastname: Perez-Rivera
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000502:physiology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: C547720:Adra1d protein, mouse; C547775:Adra2c protein, mouse; D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D020033:Protein Isoforms; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D009638:Norepinephrine