Calcium release by cholecystokinin analogue OPE is IP3 dependent in single rat pancreatic acinar cells

• Published in: The American journal of physiology Vol. 267; no. 1 Pt 1; p. C220
• Main Authors: Gaisano, H Y, Wong, D, Sheu, L, Foskett, J K
• Format: Journal Article
• Language: English
• Published: United States 01.07.1994
• Subjects: Animals; Calcium - metabolism; Carbachol - pharmacology; Cell Separation; Cholecystokinin - analogs & derivatives; Cholecystokinin - pharmacology; Inositol 1,4,5-Trisphosphate - pharmacology; Intracellular Membranes - metabolism; Male; Microinjections; Osmolar Concentration; Pancreas - cytology; Pancreas - metabolism; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction; Sincalide - analogs & derivatives; Sincalide - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1994.267.1.c220

Cholecystokinin (CCK) and carbachol raise intracellular Ca2+ concentration ([Ca2+]i) in pancreatic acinar cells by elevating inositol 1,4,5-trisphosphate (IP3). CCK analogues JMV-180 and OPE stimulate fully efficacious enzyme secretion and [Ca2+]i oscillations but release Ca2+ from intracellular stores by apparently IP3-independent mechanisms in permeabilized acinar cells. In the present study, we investigated whether OPE mobilizes Ca2+ from IP3-sensitive Ca2+ stores and whether IP3 mediates such responses in single intact cells. OPE and JMV-180 similarly 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+, depleted the same Ca2+ stores that were sensitive to OPE. In converse experiments, 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 sensitive. To determine whether IP3 mediates responses to OPE, cells were microinjected with low-molecular-weight heparin, a competitive inhibited 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-sensitive Ca2+ stores by mechanisms involving the IP3 receptor.