| 11707403 |
Caroppo R, Gerbino A, Debellis L, Kifor O, Soybel DI, Brown EM, Hofer AM, Curci S: Asymmetrical, agonist-induced fluctuations in local extracellular [Ca (2+)] in intact polarized epithelia. EMBO J. 2001 Nov 15;20(22):6316-26.
We recently proposed that extracellular Ca (2+) ions participate in a novel form of intercellular communication involving the extracellular Ca (2+)-sensing receptor (CaR). Here, using Ca (2+)-selective microelectrodes, we directly measured the profile of agonist-induced [Ca (2+)] ext changes in restricted domains near the basolateral or luminal membranes of polarized gastric acid-secreting cells. The Ca (2+)-mobilizing agonist carbachol elicited a transient, La (3+)-sensitive decrease in basolateral [Ca (2+)] (average approximately 250 microM, but as large as 530 microM). Conversely, carbachol evoked an HgCl2-sensitive increase in [Ca (2+)] (average approximately 400 microM, but as large as 520 microM) in the lumen of single gastric glands. Both responses were significantly reduced by pre-treatment with sarco-endoplasmic reticulum Ca (2+) ATPase (SERCA) pump inhibitors or with the intracellular Ca (2+) chelator BAPTA-AM. Immunofluorescence experiments demonstrated an asymmetric localization of plasma membrane Ca (2+) ATPase (PMCA), which appeared to be partially co-localized with CaR and the gastric H (+)/K (+)-ATPase in the apical membrane of the acid-secreting cells. Our data indicate that agonist stimulation results in local fluctuations in [Ca (2+)] ext that would be sufficient to modulate the activity of the CaR on neighboring cells. |
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