Two site binding of bepridil and modulation of adenylate cyclase in cardiac sarcolemmal membranes.
A preparation of cardiac sarcolemmal membranes is described. These membranes exhibit 9-24-fold purification of (Na+ + K+)-ATPase, potassium-stimulated nitrophenolphosphatase, 5'-nucleotidase, adenylate cyclase, sialic acid content, and beta-receptor number. Sarcolemmal membranes have two classes of binding sites for the calcium entry blocker, bepridil, 70 X 10(12) high-affinity sites/mg, Kd 25-40 nM; and 30 X 10(15) low-affinity sites/mg, Kd 54-70 microM. Binding of bepridil to these sites appears responsible for inhibition of isoprenaline-stimulated and activation of fluoride-stimulated adenylate cyclase. Since basal adenylate cyclase activity is not influenced, bepridil must act not at the catalytic site, but by altering the interactions between beta-receptor and catalytic and regulatory components of adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D015764:Bepridil; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002458:Cell Fractionation; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000201:enzymology*; D011759:Pyrrolidines / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D011759:Pyrrolidines; D015764:Bepridil; D000262:Adenylyl Cyclases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase