Inhibition of cardiac Na+, K+-ATPase activity by dynorphin-A and ethylketocyclazocine.
The effect of various opioids on Na+, K+ -ATPase partially purified from rat heart was examined. Dynorphin-A (1-13), dynorphin-A (1-17) and ethylketocyclazocine (EKC), which are k-type opiate agonists, markedly inhibited the enzyme activity in a dose-dependent manner; IC50 values were 12 microM, 21 microM and 0.38 mM, respectively. Morphine (mu-type agonist), methionine- and leucine-enkephalin (delta-type agonist) at the concentration of 1 mM did not affect the enzyme activity. The effect of dynorphin-A (1-13) and EKC was not antagonized by naloxone. Dynorphin-A (1-13) mainly decreased Vmax value without the change of Km value in the activation of Na+, K+-ATPase by ATP, Na+ and K+. Dynorphin-A(1-13) inhibited the partial reactions of Na+, K+-ATPase at the different degree of the potency; the inhibition of K+-stimulated phosphatase was greater than that of Na+-dependent phosphorylation. The present study suggests that dynorphin-A and EKC have an effect on cardiovascular system which is mediated by the inhibition of Na+, K+-ATPase in the heart.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016314:Ethylketocyclazocine; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D010446:Peptide Fragments; D009270:Naloxone; D016314:Ethylketocyclazocine; C026843:dynorphin (1-13); D004399:Dynorphins; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D003496:Cyclazocine; D011188:Potassium