Calcium dependence of proteinase-activated receptor 2 and cholecystokinin- mediated amylase secretion from pancreatic acini

Abstract

Pancreatic acini secrete digestive enzymes in response to a variety of secretagogues including CCK and agonists acting via proteinase-activated receptor-2 (PAR2). We employed the CCK analog caerulein and the PAR2-activating peptide SLIGRL-NH2to compare and contrast Ca2+changes and amylase secretion triggered by CCK receptor and PAR2 stimulation. We found that secretion stimulated by both agonists is dependent on a rise in cytoplasmic Ca2+concentration ([Ca2+]i) and that this rise in [Ca2+]ireflects both the release of Ca2+from intracellular stores and accelerated Ca2+influx. Both agonists, at low concentrations, elicit oscillatory [Ca2+]ichanges, and both trigger a peak plateau [Ca2+]ichange at high concentrations. Although the two agonists elicit similar rates of amylase secretion, the rise in [Ca2+]ielicited by caerulein is greater than that elicited by SLIGRL-NH2. In Ca2+-free medium, the rise in [Ca2+]ielicited by SLIGRL-NH2is prevented by the prior addition of a supramaximally stimulating concentration of caerulein, but the reverse is not true; the rise elicited by caerulein is neither prevented nor reduced by prior addition of SLIGRL-NH2. Both the oscillatory and the peak plateau [Ca2+]ichanges that follow PAR2 stimulation are prevented by the phospholipase C (PLC) inhibitor U73122, but U73122 prevents only the oscillatory [Ca2+]ichanges triggered by caerulein. We conclude that 1) both PAR2 and CCK stimulation trigger amylase secretion that is dependent on a rise in [Ca2+]iand that [Ca2+]irise reflects release of calcium from intracellular stores as well as accelerated influx of extracellular calcium; 2) PLC mediates both the oscillatory and the peak plateau rise in [Ca2+]ielicited by PAR2 but only the oscillatory rise in [Ca2+]ielicited by CCK stimulation; and 3) the rate of amylase secretion elicited by agonists acting via different types of receptors may not correlate with the magnitude of the [Ca2+]irise triggered by those different types of secretagogue.