title: Gap junction communication modulates [Ca2+]i oscillations and enzyme secretion in pancreatic acini.
abstract: Global (all cells in an acinus) and focal (1-2 out of 10-15 cells) stimulation of pancreatic acini with bombesin or t-butyloxycarbonyl-Tyr(SO3)-Nle-Gly-Tyr-Asp-2-phenylethyl ester (CCKJ) together with modulation of gap junction (GJ) permeability by octanol and NO2- was used to study the role of GJ permeability in controlling [Ca2+]i oscillations and enzyme secretion. GJ permeability was quantitated by measuring fluorescence recovery after photobleaching. Octanol at 0.5 mM markedly reduced, whereas 15 mM NO2- increased GJ permeability. Focal application of bombesin caused synchronized oscillations in the entire acinus, whereas global stimulation resulted in asynchronous oscillations. Increasing GJ permeability with NO2- had no effect on bombesin-evoked [Ca2+]i oscillations. Octanol inhibited ongoing oscillations evoked by focal or global bombesin stimulation. However, when GJ were blocked prior to stimulation, subsequent global stimulation with bombesin induced long-lasting oscillations in all cells. Re-establishing GJ communication for as little as 37.5 s conferred GJ dependence on the order and time of [Ca2+]i spiking evoked by global bombesin stimulation. Focal and global stimulation with CCKJ gave different patterns of [Ca2+]i oscillations. However, in contrast to bombesin, inhibition of GJ with octanol had no effect on oscillations induced by global CCKJ stimulation. Increasing GJ permeability with NO2- synchronized CCKJ-stimulated oscillations by equalizing the amplitude and increasing the frequency in all cells within an acinus. These observations suggest that amplitude and frequency of [Ca2+]i oscillations can be regulated independently of each other, and that GJ permeable molecules modulate the frequency of [Ca2]i oscillation in an agonist-specific manner. Regardless of the agonist, increasing the frequency of oscillations by modulation of GJ permeability correlated with an increased enzyme secretion.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
authors.forename: P L
authors.initials: PL
authors.lastname: Stauffer
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: K
authors.initials: K
authors.lastname: Luby-Phelps
authors.forename: R L
authors.initials: RL
authors.lastname: Moss
authors.forename: R A
authors.initials: RA
authors.lastname: Star
authors.forename: S
authors.initials: S
authors.lastname: Muallem
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002463:Cell Membrane Permeability; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000378:metabolism*; D007700:Kinetics; D000442:Octanols / Q000494:pharmacology; D009991:Oscillometry; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D000442:Octanols; C083006:t-butyloxycarbonyl-sulfotyrosyl-norleucyl-glycyl-tyrosyl-aspartyl-2-phenylethyl ester; D002766:Cholecystokinin; D001839:Bombesin; D002118:Calcium; D016257:Fura-2