title: Calcium influx pathways in rat pancreatic ducts.
abstract: A number of agonists increase intracellular Ca2+ activity, [Ca2+]i, in pancreatic ducts, but the influx/efflux pathways and intracellular Ca2+ stores in this epithelium are unknown. The aim of the present study was to characterise the Ca2+ influx pathways, especially their pH sensitivity, in native pancreatic ducts stimulated by ATP and carbachol, CCH. Under control conditions both agonists led to similar changes in [Ca2+]i. However, these Ca2+ transients, consisting of peak and plateau phases, showed different sensitivities to various experimental manoeuvres. In extracellular Ca2+-free solutions, the ATP-induced [Ca2+]i peak decreased by 25%, but the CCH-induced peak was unaffected; both plateaus were inhibited by 90%. Flufenamate inhibited the ATP-induced peak by 35%, but not the CCH-evoked peak; the plateaus were inhibited by 75-80%. La3+ inhibited the ATP-induced plateau fully, but that induced by CCH by 55%. In resting ducts, an increase in extracellular pH, pHe, by means of HEPES and HCO3-/CO2 buffers, increased [Ca2+]i; a decrease in pHe had the opposite effect. In stimulated ducts the pH-evoked effects on Ca2+ influx were more pronounced and depended on the agonist used. At pHe 6.5 both ATP- and CCH-evoked plateaus were inhibited by about 50%. At pH 8.0 the ATP-stimulated plateau was inhibited by 27%, but that stimulated by CCH was increased by 72%. Taken together, we show that CCH stimulates Ca2+ release followed by Ca2+ influx that is moderately sensitive to flufenamate, La3+, depolarisation, it is inhibited by low pH, but stimulated by high pH. ATP stimulates Ca2+ release and probably an early Ca2+ influx, which is more markedly sensitive to flufenamate and La3+, and is both inhibited by low and high pH. Thus our study indicates that there are at least two separate Ca2+ influx pathways in pancreatic ducts cells.
authors.affiliation: Physiologisches Institut, Albert-Ludwigs-Universität, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hug
authors.forename: C
authors.initials: C
authors.lastname: Pahl
authors.forename: I
authors.initials: I
authors.lastname: Novak
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D005439:Flufenamic Acid; D002217:Carbachol; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium