Interaction between alpha(1)- and alpha(2)-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries.
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.
Sporkova
Alexandra
A
Institute for Clinical and Experimental Medicine, Prague, Czech Republic. alhc@medicon.cz
Perez-Rivera
Alex
A
Galligan
James J
JJ
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*
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