Role of cAMP in the effects of K+ on the steroidogenesis of zona glomerulosa cells

1. Investigations of the role of cAMP in the stimulation of the steroidogen esis of zona glomerulosa (ZG) cells by increased extracellular K+ concentra tion are reviewed. 2. Possible reasons for discrepancies in the results of different investiga tors on whether K+ increases the cAMP content or output of ZG tissue or dis persed cells are discussed. 3. The concentration of cAMP in the incubating media of ZG tissue or cells, rather than their cAMP content, seems to respond more sensitively to stimu lation by extracellular K+, as was also found for adrenocorticotropic hormo ne stimulation of zona fasciculata-reticularis cells. 4. The addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanth ine (IBMX) to incubations with the aim of increasing the sensitivity of the response in cAMP to extracellular K+ in ZG cells may give rise to effects, probably nonspecific, which actually inhibit the measured response, 5. The immediate stimulation in the steroidogenesis of ZG cells with raised extracellular K+ is probably mostly due to the direct effect of increases in cytoplasmic Ca2+ (arising from increases in Ca2+ influx) on mitochondria l processes, However, increases in cAMP may prolong the stimulation of ster oidogenesis by increased extracellular K+. This increased cAMP is probably due to stimulation of adenylyl cyclase activity. 6. It has been concluded that the increase in Ca2+ influx output after rise s in the extracellular K+ concentration of ZG cells is responsible for most of the increase in cAMP. 7. According to one group of investigators, there is weak stimulation of ph ospholipase C (PLC) activity after increasing the extracellular K+ concentr ation of rat ZG cells. 8. If there is such a stimulation of PLC activity, it seems that the action of increased extracellular K+ can potentially involve all known mechanisms for the stimulation of steroidogenesis in endocrine cells. The common prim ary event is probably the increase in Ca2+ influx. The relative importance of these various potential mechanisms may depend on the particular in vitro conditions used.