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J. Biol. Chem., Vol. 277, Issue 11, 9016-9021, March 15, 2002

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Stimulation of Cl Secretion via Membrane-restricted Ca²⁺ Signaling Mediated by P2Y Receptors in Polarized Epithelia^*

Connie Hau-Yan Wong and Wing-hung Ko

From the Department of Physiology, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong, China

Extracellular nucleotides such as ATP have been shown to regulate ion transport processes in a variety of epithelia. This effect is mediated by the activation of plasma membrane P2Y receptors, which leads to Ca²⁺ signaling cascade. Ion transport processes (e.g. activation of apical calcium-dependent Cl channels) are then stimulated via an increase in [Ca²⁺]_i. Many polarized epithelia express apical and/or basolateral P2Y receptors. To test whether apical and basolateral stimulation of P2Y receptors elicit polarized Ca²⁺ signaling and anion secretion, we simultaneously measured the two parameters in polarized epithelia. Although activation of P2Y receptors located at both apical and basolateral membranes evoked an increase in [Ca²⁺]_i, only apical P2Y receptors-coupled Ca²⁺ release stimulated an increase in anion secretion. Moreover, the calcium influx evoked by apical and basolateral P2Y receptor stimulation is predominately via the basolateral membrane domain. It appears that the apical P2Y receptor-regulated Ca²⁺ release and activation of apical Cl channels is compartmentalized in polarized epithelia with basolateral P2Y-stimulated Ca²⁺ release failing to activate anion secretion. These data suggest that there may be two distinct ATP-releasable Ca²⁺ pools, each coupled to apical and basolateral membrane receptor but linked to the same calcium influx pathway located at the basolateral membrane.

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