Calcium influx and intracellular stores in angiotensin II stimulation of normal and hyperplastic pituitary cells.
In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke a clear spike elevation of intracellular Ca2+ concentration ([Ca2+]i) but induces a plateau increase. The present work was undertaken to establish whether this difference was related to a differential participation of intracellular and/or plasma membrane Ca2+ channels. We first tested the effect of 10 nM ANG II on [Ca2+]i in the absence of extracellular Ca2+ in cells depolarized with 25 mM K+ or in the presence of blockers of L-type voltage-sensitive Ca2+ channels (VSCC). These treatments did not alter spike elevation in [Ca2+]i in controls but reduced plateau levels in hyperplastic cells. Intracellular Ca2+ stores were similar in both groups, as assessed by thapsigargin treatment, but this drug abolished spike increase in controls and scarcely modified plateau levels in hyperplastic cells. Finally, inositol trisphosphate (InsP3) production in response to ANG II was significantly higher in control cells. We conclude that the observed plateau rise in hyperplastic cells results mainly from Ca2+ influx through VSCC. In contrast, in control cells, the ANG II-induced spike increase in [Ca2+]i results from mobilization of Ca2+ from thapsigargin-sensitive internal channels, activated by higher inositol 1,4,5-trisphosphate generation.
Iglesias
A G
AG
Instituto de Biología y Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, 1428 Buenos Aires, Argentina.
Diaz-Torga
G
G
Lux-Lantos
V
V
Libertun
C
C
Becu-Villalobos
D
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D005260:Female; D006965:Hyperplasia; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000804:Angiotensin II; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D011188:Potassium; D002118:Calcium