Effects of caffeine on the influx of extracellular calcium in GH4C1 pituitary cells

✍ Scribed by Leena Karhapää; Kid Törnquist

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 191 KB
• Volume: 171
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199704)171:1<52::aid-jcp7>3.0.co;2-g

✦ Synopsis

Caffeine increases intracellular Ca 2/ concentrations ([Ca 2/ ] i ) in a variety of cell types by triggering the mobilization of Ca 2/ from intracellular Ca 2/ stores. Caffeine also can change [Ca 2/ ] i by affecting Ca 2/ influx through voltage-operated Ca 2/ channels (VOCCs). In the present study, we investigated the effects of caffeine on Ca 2/ entry in GH 4 C 1 pituitary cells. Pretreatment of the cells with caffeine attenuated the high K / -evoked influx of 45 Ca 2/ in a dose-dependent manner. This inhibition was not secondary to the caffeine-evoked elevation of [Ca 2/ ] i because caffeine was able to inhibit VOCCs also in the presence of the intracellular Ca 2/ chelator BAPTA. However, the inhibitory effect of caffeine on 45 Ca 2/ entry appeared to be dependent on the degree of depolarization of the plasma membrane. Only in cells depolarized with relatively high concentrations of K / (20, 35, and 50 mM) was the caffeine-induced inhibition observed. A similar inhibitory effect of caffeine on the high K / -evoked calcium and barium entry was observed in experiments using Fura 2. Neither IBMX, forskolin nor dibutyryl cAMP reduced the enhanced [Ca 2/ ] i induced by 50 mM K / , suggesting that the effect of caffeine was not due to increased intracellular cAMP. Furthermore, high doses of caffeine inhibited the plateau level of the TRH-induced increase in [Ca 2/ ] i , which is caused partly by influx of Ca 2/ through VOCCs. The inhibitory effect of caffeine was, in part, due to an hyperpolarization of the plasma membrane observed at high doses of caffeine. On the other hand, low doses of caffeine enhanced depolarization-evoked Ba 2/ entry as well as the TRH-evoked plateau level of [Ca 2/ ] i . We conclude that caffeine has a dual effect on Ca 2/ entry through activated VOCCs in GH 4 C 1 cells: at low concentrations caffeine enhances Ca 2/ entry, whereas high concentrations of caffeine block Ca 2/ entry.