Secretin stimulates $${\rm HCO}_{\rm 3}^{\rm - } $$ and acetate efflux but not Na + / $${\rm HCO}_{\rm 3}^{\rm - } $$ uptake in rat pancreatic ducts

Abstract

Pancreatic ducts secrete HCO3(-), but transport mechanisms are unresolved and possibly vary between species. Our aim was to study the intracellular pH (pHi) regulation and thus H+/HCO3- transport in rat pancreatic ducts. Of particular interest was the Na+/HCO3(-) cotransporter, thought to be important in HCO3(-) -transporting epithelia. pHi was measured with BCECF in freshly isolated intralobular ducts. A reduction in extracellular Na+ concentration or application of HOE 694 (1 microM) decreased pHi by 0.1 to 0.6 pH units, demonstrating Na+/H+ exchanger activity. A reduction in extracellular Cl- concentration or addition of H2DIDS (10 microM) increased pHi by 0.1 to 0.5 pH units, demonstrating Cl-/ HCO(3)- (OH ) exchanger activity. In experimental acidosis, extracellular HCO3(-)/CO2 buffer did not increase the rate of pHi recovery, indicating that provision of HCO3(-) by the Na+/HCO3(-) cotransporter was not apparent. Most importantly, Na+/HCO3(-) cotransport was not stimulated by secretin (1 nM). In contrast, in experimental alkalosis the pHi recovery was increased in HCO3(-)/CO2 buffer, possibly due to Na+/HCO3(-) cotransport in the efflux mode. Secretin (1 nM) and carbachol (1 microM) stimulated HCO3(-) efflux, which can account for the observed HCO3(-) concentrations in rat pancreatic juice. Acetate and HCO3(-) buffers were handled similarly, indicating similar transport mechanisms in pancreatic ducts.

Protein kinase C mediates the inhibitory effect of substance P on HCO3− secretion from guinea pig pancreatic ducts

“…5B). A modest, 1.4-fold stimulatory effect of secretin on pH i recovery after an alkali load also has been reported in rat pancreatic duct cells (37). Figure 5B shows that secretinstimulated ϪJ(B Ϫ ) was completely inhibited by 20 nM SP (n ϭ 6) and that the same effect was observed with 100 nM PDBu (n ϭ 7).…”

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

“…A modest 1.4-fold stimulatory effect of secretin on pH i recovery after an alkali load has also been reported in rat pancreatic duct cells (22). In contrast, secretin had no effect on ϪJ(B Ϫ ) when the experiments were performed in a Cl Ϫ -free medium, indicating that the hormone activates a Cl Ϫ -dependent HCO 3 Ϫ transport mechanism in the duct cell.…”

“…As expected, neither SP nor secretin had any effect on the initial J(B Ϫ ) of recovery from an acid load, providing evidence that these peptides do not directly modulate the activity of the basolateral base-loading transporters. Secretin also has no significant effect on pH i recovery from an acid load in rat pancreatic duct cells (22).…”

Effect of ATP on Intracellular pH in Pancreatic Ducts Involves P2X₇ Receptors

“…1A is an example of one such experiment and shows that ATP within about 1 min caused a small and reversible decrease in pH i in both +BIC and -BIC solutions. The figure also shows that the resting pH i was lower in ducts exposed to +BIC compared to -BIC solutions, due to hydration of CO 2 entering cells from the HCO 3 -/CO 2 buffer, as also observed earlier [22]. The measurement was completed by an ammonium pulse to see if the duct was responding as expected, that is, cells alkalinized with ammonium and acidified when ammonium was removed.…”

“…Electrophysiological studies on rat pancreatic ducts show that secretagogoues such as secretin, acetylcholine or β-adrenergic agonists initiate secretory processes by: opening of the luminal Cl -channels; opening of the basolateral K + channels that keep the driving force; and by coordinating the action of one or more of the H + /HCO 3 -transporters [15][16][17]. Pancreatic ducts express on the basolateral membrane NHE and possibly Na + -HCO 3 -cotransporter (NBC), which would lead to accumulation of cellular HCO 3 - [18][19][20][21][22]. On the luminal membrane AE, or another anion exchanger of the sulphate permease family, such as SLC26A6 or DRA, would allow efflux of HCO 3 -into the lumen [15,23,24].…”