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HORMONES AND SIGNALING

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

¹Department of Surgery, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts; and ²Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts

Submitted 30 July 2004 ; accepted in final form 17 June 2005

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-NH₂ to 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⁺]_i reflects both the release of Ca²⁺ from intracellular stores and accelerated Ca²⁺ influx. Both agonists, at low concentrations, elicit oscillatory [Ca²⁺]_i changes, and both trigger a peak plateau [Ca²⁺]_i change at high concentrations. Although the two agonists elicit similar rates of amylase secretion, the rise in [Ca²⁺]_i elicited by caerulein is greater than that elicited by SLIGRL-NH₂. In Ca²⁺-free medium, the rise in [Ca²⁺]_i elicited by SLIGRL-NH₂ is 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⁺]_i changes that follow PAR2 stimulation are prevented by the phospholipase C (PLC) inhibitor U73122, but U73122 prevents only the oscillatory [Ca²⁺]_i changes triggered by caerulein. We conclude that 1) both PAR2 and CCK stimulation trigger amylase secretion that is dependent on a rise in [Ca²⁺]_i and that [Ca²⁺]_i rise 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⁺]_i elicited by PAR2 but only the oscillatory rise in [Ca²⁺]_i elicited 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⁺]_i rise triggered by those different types of secretagogue.

caerulein; phospholipase C

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