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HORMONES AND SIGNALING

Luminal adenosine stimulates chloride secretion through A₁ receptor in mouse jejunum

¹Department of Cell Physiology, Free University of Brussels, Brussels, Belgium; ²Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; ³Institute of Interdisciplinary Research, Free University of Brussels, Brussels; ⁴Department of Medical Chemistry, Erasme Hospital, Free University of Brussels, Brussels; and ⁵Department of Physiology, Katholieke Universiteit Leuven, Leuven, Belgium

Submitted 2 August 2004 ; accepted in final form 27 December 2004

Adenosine is known to stimulate chloride secretion by mouse jejunum. Whereas the receptor on the basolateral side is believed to be A_2B, the receptor involved in the luminal effect of adenosine has not been identified. We found that jejuna expressed mRNA for all adenosine receptor subtypes. In this study, we investigated the stimulation of chloride secretion by adenosine in jejuna derived from mice lacking the adenosine receptors of A₁ (A₁R) and A_2A (A_2AR) or control littermates. The jejunal epithelium was mounted in a Ussing chamber, and a new method on the basis of impedance analysis was used to calculate the short-circuit current (I_sc) values. Chloride secretion was assessed by the I_sc after inhibition of the sodium-glucose cotransporter by adding phloridzin to the apical bathing solution. The effect of apical adenosine on chloride secretion was lost in jejuna from mice lacking the A₁R. There was no difference in the response to basolaterally applied adenosine or to apical forskolin. Furthermore, in jejuna from control mice, the effect of apical adenosine was also abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine, a specific A₁R antagonist. Responses to adenosine were identical in jejuna from control and A_2AR knockout mice. This study demonstrates that A₁R (and not A_2AR) mediates the enhancement of chloride secretion induced by luminal adenosine in mice jejunum.

intestinal secretion; diarrhea; chloride channels

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