Identification of an angiotensin receptor in rabbit renomedullary interstitial cells in tissue culture. Correlation with prostaglandin biosynthesis.
High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociation constant of 3.1 mM. The binding inhibition activities of analogues of angiotensin II correlated with their biological potencies: [Sar1, Ala8]A II greater than [des-Asp1]A II greater than greater than 3--8 hexapeptide. The biologically inactive 1--7 heptapeptide failed to displace the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin E2 biosynthesis by the rabbit renomedullary interstitial cells in tissue culture. The concentration of angiotensin II that resulted in half maximal stimulation of prostaglandin E2 biosynthesis (6.5 nM) correlated with the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). The relative potency of [des-Asp1] A II as a stimulus for prostaglandin E2 biosynthesis was proportional to its relative binding inhibition activity. These findings demonstrate the biological significance of the angiotensin II binding sites in the rabbit renomedullary interstitial cells in tissue culture and suggest that the cells may provide a homogeneous model tissue for the study of the angiotensin receptor.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D046508:Culture Techniques; D004229:Dithiothreitol / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007679:Kidney Medulla; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface
D007457:Iodine Radioisotopes; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D010664:Phenylmethylsulfonyl Fluoride; D004229:Dithiothreitol