Cyclic AMP stimulation of Na-K pump activity in quiescent Swiss 3T3 cells

✍ Scribed by Sonia Paris; Enrique Rozengurt

• Publisher: John Wiley and Sons
• Year: 1982
• Tongue: English
• Weight: 1008 KB
• Volume: 112
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041120217

✦ Synopsis

Abstract

Recently, we have found that an increase in the intracellular level of cAMP acts as a mitogenic signal for Swiss 3T3 cells (Rozengurt et al., Proc. Natl. Acad. Sci. USA, 78:4392, 1981). The results presented in this paper demonstrate that addition of cAMP‐elevating agents to confluent and quiescent cultures of Swiss 3T3 causes a marked increase in the rate of ^86^Rb+ uptake but has no effect on the rate of cation efflux. The stimulation of ion uptake is mediated by the Na‐K pump as shown by the ouabain sensitivity of the ^86^Rb+ fluxes. The increase in Na‐K pump activity occurs whether cAMP is generated endogenously by stimulation of adenylate cyclase activity by cholera toxin, adenosine agonists, or PGE~1~ or added exogenously as 8BrcAMP. The stimulatory effect of these compounds on ^86^Rb+ uptake is potentiated by inhibitors of cyclic nucleotide phosphodiesterase activity. Cholera toxin stimulates the Na‐K pump in a dose‐dependent manner; half‐maximal effect is achieved at 0.7 ng/ml.

The stimulation of ouabain‐sensitive ^86^Rb+ uptake by cAMP‐elevating agents reaches a maximum after 2‐3 h of incubation. This contrasts with the rapid (within minutes) stimulation of the Na‐K pump caused by serum and other mitogenic agents. Further, cAMP‐elevating agents fail to increase in Na+ influx, under identical experimental conditions. These findings suggest that the stimulation of Na‐K pump activity caused by increased cAMP levels contrasts mechanistically with the rapid control of pump activity by serum which is primarily mediated by increased Na+ entry into the cells.