Heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein.
To understand the subtypes of alpha 1-adrenoceptors in the regulation of uterine and umbilical vascular function, the subtypes of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein were investigated pharmacologically. The use of the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine, revealed the heterogeneity of alpha 1-adrenoceptors in these two tissues. Chloroethylclonidine showed different patterns of action. While it depressed the maximal contraction to norepinephrine in the umbilical vein, it did not decrease the maximal response in the uterine artery. The alpha 1A-adrenoceptor antagonist, 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (WB 4101), competitively inhibited norepinephrine-induced contractile responses in the ovine uterine artery and umbilical vein with intermediate pA2 values of 8.30 and 8.45, respectively. Combined use of chloroethylclonidine with either prazosin or WB 4101 produced an additive inhibition of norepinephrine-induced contractions in both tissues, suggesting an interaction of WB 4101 with a chloroethylclonidine-insensitive alpha 1-adrenoceptor. However, the chloroethylclonidine-insensitive alpha 1-adrenoceptor differed on the affinity for prazosin in the uterine artery and umbilical vein. The Ca2+ channel blocker, nifedipine, inhibited contractions to both the chloroethylclonidine-sensitive alpha 1-adrenoceptor (alpha 1B subtype) and the chloroethylclonidine-insensitive alpha 1-adrenoceptor in both tissues. Prazosin, WB 4101 and chloroethylclonidine all inhibited norepinephrine-induced contraction due to the release of calcium from intracellular stores in both tissues. Our results suggest that there is heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein. Both the chloroethylclonidine-sensitive and insensitive alpha 1-adrenoceptor may use both intracellular and extracellular Ca2+ sources.
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Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
Dyer
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009543:Nifedipine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin