Modulation of Na, K-ATPase activity by prostaglandin E1 and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin.

Abstract

Adenylyl cyclase is activated by prostaglandin E and inhibited by mu-opioids. Since cAMP-related events influence the activity of the Na Pump and its biochemical correlate Na,K-ATPase in many systems, we tested the hypothesis that prostaglandin E1 and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a mu-opioid agonist, have opposing actions on Na,K-ATPase activity. Studies were conducted with alamethicin-permeabilized SH-SY5Y human neuroblastoma cells. Prostaglandin E1 (1 microM) transiently inhibited Na,K-ATPase activity for 10-15 min. A direct activator of protein kinase A, 8-Br-cAMP (150 and 500 microM), also inhibited, but more rapidly and for a shorter duration. Both DAMGO (1 microM) and Rp-adenosine 3',5'-cyclic monophosphorothioate (500 microM), a protein kinase A-inhibitor, reversed the inhibitory effect of prostaglandin E1. DAMGO alone (1 microM) stimulated Na,K-ATPase activity up to nearly three-fold control activity. The stimulatory action of DAMGO was blocked by cyclosporine A (2 microM), an inhibitor of calcineurin, and was dependent on Ca2+ entry through nifedipine-sensitive Ca2+ channels. In the presence of 1 mM EGTA, DAMGO inhibited Na,K-ATPase activity. DAMGO-induced inhibition was blocked by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C (1 microM). Na,K-ATPase is poised to modulate neuronal excitability through its roles in maintaining the membrane potential and transmembrane ion gradients. The differential effects of prostaglandin E1 and opioids on Na,K-ATPase activity may be related to their actions in hyperalgesia.

• Authors: Karen Woolcock, Susan C Specht
• Journal: Life sciences (Life Sci) Vol. 78 Issue 15 Pg. 1653-61 (Mar 06 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16460765 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Calcium Channels, L-Type
• Enzyme Inhibitors
• Receptors, Opioid, mu
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Cyclic AMP
• Sodium-Potassium-Exchanging ATPase
• Alprostadil

Topics

• Alprostadil (pharmacology)
• Calcium Channels, L-Type (metabolism)
• Cell Line, Tumor
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Drug Interactions
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)- (pharmacology)
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Humans
• Receptors, Opioid, mu (agonists)
• Signal Transduction (drug effects)
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, metabolism)