Canine mesenteric artery Na+,K+-ATPase: vasopressor receptor for digitalis?
Localization and characterization studies of Na+,K+-ATPase in canine superior mesenteric artery were undertaken to examine the role of the Na+-K+ pump in the vasopressor response of cardiac glycosides. The enzymatic component of the membrane-bound Na+-K+ pump, Na+,K+-ATPase, was found by histochemical and cell fractionation techniques to be localized primarily in the sarcolemma of the smooth muscle cell in superior mesenteric artery. The enzyme could be enriched in microsomal and partially purified sarcolemma preparations of superior mesenteric artery and first-order arterial side branches. Binding of [3H]ouabain to arterial microsomes followed pseudo-first-order reaction kinetics. In the presence of magnesium plus ATP, sodium stimulates and potassium inhibits the rate of binding. Scatchard analysis indicated a single class of [3H]ouabain binding sites with a KD of 2-9 nM and a Bmax of 2.3-3.5 pmol/mg protein. Although the characteristics of [3H]ouabain binding to mesenteric artery microsomes resemble the characteristics of [3H]ouabain binding to purified Na+,K+-ATPase, the density or total number of Na+-K+ pump sites in mesenteric artery is small compared with either heart muscle or kidney parenchyma. In isolated mesenteric arterial strips, more than 80% of a 2.5 microM ouabain-induced contraction could be inhibited or reversed by alpha-adrenoceptor blockade with 1 microM phentolamine. These data indicate that although cardiac glycosides interact with specific receptor sites in smooth muscle of canine superior mesenteric artery, the direct vasoconstrictor effect, which may be related to this digitalis-smooth muscle Na+,K+-ATPase interaction, is meager and may be a reflection of the low density of Na+-K+ pump sites.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011955:Receptors, Drug / Q000032:analysis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D011955:Receptors, Drug; C027082:digitalis receptor; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D010646:Phentolamine