CALCIUM-RELEASE BY CHOLECYSTOKININ ANALOG OPE IS IP3 DEPENDENT IN SINGLE-RAT PANCREATIC ACINAR-CELLS

Citation
Hy. Gaisano et al., CALCIUM-RELEASE BY CHOLECYSTOKININ ANALOG OPE IS IP3 DEPENDENT IN SINGLE-RAT PANCREATIC ACINAR-CELLS, The American journal of physiology, 267(1), 1994, pp. 30000220-30000228
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
ISSN journal
0002-9513
Volume
267
Issue
1
Year of publication
1994
Part
1
Pages
30000220 - 30000228
Database
ISI
SICI code
0002-9513(1994)267:1<30000220:CBCAOI>2.0.ZU;2-9
Abstract
Cholecystokinin (CCK) and carbachol raise intracellular Ca2+ concentra tion ([Ca2+](i)) in pancreatic acinar cells by elevating inositol 1,4, 5-trisphosphate (IP3). CCK analogues JMV-180 and OPE stimulate fully e fficacious enzyme secretion and [Ca2+](i) oscillations but release Ca2 + from intracellular stores by apparently IP3-independent mechanisms i n permeabilized acinar cells. In the present study, we investigated wh ether OPE mobilizes Ca2+ from IP3-sensitive Ca2+ stores and whether IP 3 mediates such responses in single intact cells. OPE and JMV-180 simi larly elevated IP3 to low levels compared with those elicited by 10 nM CCK. Depletion of IP3-sensitive stores by elevation of intracellular IP3 using carbachol, microinjection of a nonmetabolizable IP3 analogue , or exposure to thapsigargin, in the absence of extracellular Ca2+, d epleted the same Ca2+ stores that were sensitive to OPE. In converse e xperiments, OPE depleted carbachol- or thapsigargin-sensitive stores, indicating that carbachol-, thapsigargin-, IP3-, and OPE-sensitive Ca2 + stores overlap completely and that stores mobilized by OPE are IP3 s ensitive. To determine whether IP3 mediates responses to OPE, cells we re microinjected with low-molecular-weight heparin, a competitive anta gonist of IP3 binding to the IP3 receptor. Heparin competitively inhib ited the rise of [Ca2+](i) in response to carbachol, OPE, or JMV-180, whereas de-N-sulfated heparin, an inactive heparin, was without effect . These results indicate that CCK analogues release Ca2+ from IP3-sens itive Ca2+ stores by mechanisms involving the IP3 receptor.