Mechanisms of hypercapnia-stimulated PG production in piglet cerebral microvascular endothelial cells.
High CO2 stimulates dilator prostanoid (prostaglandin; PG) synthesis by piglet cerebral microvascular endothelial cells, but the mechanism of stimulation is unclear. We address the hypothesis that intracellular pH (pHi) and Ca2+ signaling are involved. When extracellular pH (pHe) and PCO2 were constant and pHi was rapidly reduced (propionate or nigericin), PG synthesis was stimulated. When pHe was lowered by reducing NaHCO3, pHi fell slowly, but PG synthesis was not altered. When pHe was decreased by increasing PCO2 or returned to 7.4 by increasing NaHCO3, with a constant PCO2 of 100 mmHg, pHi dropped quickly and PG synthesis was stimulated. When pHi was reduced slowly by changing CO2 slowly, or by stepwise addition of propionate, PG synthesis was increased regardless of pHe, suggesting that the rapid decline of pHi plays a central role in mediating the PG synthesis. Ca2+ signaling is a potential mechanism by which pHi increases PG synthesis. However, extracellular Ca2+ removal did not affect PG synthesis induced by propionate or hypercapnia. Furthermore, neither rapid nor slow decreases of pHi altered cytosolic free Ca2+ concentration. Therefore, Ca2+ signals do not appear to be involved in the CO2 stimulation of PG synthesis.
Hsu
P
P
Department of Physiology/Biophysics, University of Tennessee, Memphis 38163.
Albuquerque
M L
ML
Leffler
C W
CW
D000143:Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism; D008833:Microcirculation; D009550:Nigericin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D013552:Swine
D000143:Acids; D011422:Propionates; D011453:Prostaglandins; D002245:Carbon Dioxide; C029658:propionic acid; D009550:Nigericin; D002118:Calcium