Angiotensin receptors and the control of Na+ and K+ transport in cultured aortic smooth muscle and brain microvessel cells.
We examined the effect of angiotensin on Na+ and K+ transport by cultures of aortic smooth muscle and brain microvessel cells. Angiotensin II (AII) and angiotensin III (AIII) stimulated net Na+ uptake, which was assayed in the presence of ouabain to block Na+ efflux via the Na+-K+ pump. The combination of saturating concentrations of AII and AIII produced no greater stimulation of net Na+ uptake than either angiotensin by itself. AII also stimulated ouabain-sensitive 86Rb+ uptake by cultured aortic smooth muscle and brain microvessel cells. AII was not as effective as monensin, a Na+ ionophore, in stimulating the Na+-K+ pump. In the presence of monensin, AII had no effect on ouabain-sensitive 86Rb+ uptake. These data are consistent with previous observations suggesting that AII stimulates the Na+-K+ pump by supplying it with more of its rate-limiting substrate, Na+. 125I-AII bound tightly to cultured aortic muscle cells. Approximately 5 nM unlabelled AII half-maximally inhibited 125I-AII binding. Incubation of intact cultures with 1.0 microM AII produced a time-dependent decrease in specific 125I-AII binding. This slow loss of AII binding was prevented by methylamine, a known inhibitor of receptor clustering and internalization. We conclude (1) that angiotensin increases the Na+ permeability of smooth muscle cells in culture, thereby stimulating the Na+-K+ pump; (2) that AII binds to a specific receptor on the cell surface; and (3) that the AII-receptor complex may be internalized by a methylamine-inhibited pathway.
D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D008833:Microcirculation / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D000809:Angiotensins; D000804:Angiotensin II; D000805:Angiotensin III; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase