Luminal adenosine stimulates chloride secretion through A₁receptor in mouse jejunum

Abstract

sine is known to stimulate chloride secretion by mouse jejunum. Whereas the receptor on the basolateral side is believed to be A2B, 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 A2A (A2AR) 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 A 1R. 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 A 1R 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 ADENOSINE IS AN ENDOGENOUS nucleoside that can regulate a large number of physiological and pathophysiological processes (4, 9 -16, 18, 24, 25, 31). Adenosine is generated by hydrolysis of intra-or extracellular adenine nucleotides (11).

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

“…The earliest descriptions of the prosecretory effect of ADO in intestine were reported in 1984, in which basolateral addition of ϳ0.5 to 1.0 mM ADO to chambered rabbit ileum or colon in vitro elicited an increase in electrogenic net Cl Ϫ secretion (Dobbins et al, 1984;Grasl and Turnheim, 1984). More recently, numerous groups have reported the prosecretory effects of ADO in cultured epithelial cells or mounted intestinal tissues through the activation of A 2 or A 1 receptors, respectively (Ghanem et al, 2005;Novak et al, 2008;Wang et al, 2008;Rajagopal and Pao, 2010).…”

“…Most of the research regarding extracellular ADO signaling in the gut has addressed enteric neurons, smooth muscle, afferent neurons, and the immune system, with relatively few studies addressing its effect on epithelial secretory function. Of these, even fewer have reported the effect of luminal ADO on ion secretion in intact epithelia in vivo, because most published studies reported short-circuit current (I sc ) measured in intestinal T84 monolayers (Barrett et al, 1989;Strohmeier et al, 1995) or mounted mammalian intestinal tissues (Dobbins et al, 1984;Grasl and Turnheim, 1984;Ghanem et al, 2005). Because apical or basolateral ADO stimulated I sc , ADO receptors were predicted to be expressed on both epithelial surfaces (Barrett et al, 1989;Strohmeier et al, 1995).…”

Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

“…In the airway epithelia, it seems that A 2B receptors regulate Cl − secretion and A 2A/B receptors regulate Na + absorption [3,7,15]. In the small intestine, luminal A 1 receptors stimulate Cl − secretion [12], and in the colon, the A 2B receptors are expressed on the luminal and basolateral membrane and stimulate Cl − secretion [35,37].…”

Purinergic receptors in gastrointestinal inflammation

“…In addition to its effect on immune cell migration and function, A1 receptor has been shown to play a significant role in luminal adenosine-induced chloride secretion in human jejunum (54). In a study using rigorous electrophysiological techniques, the investigators demonstrated that luminal adenosine-induced chloride secretion was mediated by A1 receptor even though A2b receptor was the most abundant adenosine receptor expressed in jejunal mucosa.…”

“…Esophagus, stomach, duodenum, jejunum, colon, cecum (124) (54,84), involved in enteric neuronal function (10) ?…”