Purinergic Signalling (2012) 8 (Suppl 1):S61–S79 regions of the distal colon (Fig. 3). Immunostaining was specific since the pre-incubation of each antibody with its respective peptide antigen abolished all immunoreactivity. P2Y1 was co-localized with α-smooth actin, indicating that it is expressed in vascular and enteric smooth muscle cells (Fig. 3a). It also displayed a muscular localization, although its expression did not overlap that of S-100. P2Y2 was detected in myenteric neurons (Fig. 3b), P2Y4 was detected in enteric glial cells (Fig. 3c), P2Y6 was shown to be expressed in vascular and enteric smooth muscle cells (Fig. 3d), P2Y11 in enteric glial cells (Fig. 3e), and P2Y12 was detected in enteric nerves (Fig. 3f). The study further showed that more than one P2 receptor subtype is involved S67 in purinergic relaxation of the circular muscle of the rat distal colon. The duodenum secretes HCO3− which is in part responsible for protecting the upper GI tract from gastric acid. Intestinal alkaline phosphatase (IAP) expressed along the brush border has been shown to work at alkaline pH and has an ATPase activity, although its exact function is unknown. What is known, however, is that increased secretion of HCO3− by extracellular ATP enhances the enzyme’s activity, suggesting a negative feedback loop. The authors show that ATP is indeed a substrate for IAP activity [31]. In addition, the inhibition of IAP leads to the release of ATP, which activates purinergic receptors in the Fig. 3 Expression of P2Y receptors in rat distal colon. All P2Y immunohistochemical staining was done using Alomone Labs anti-P2Y receptor antibodies. a Double immunolabeling reveals that P2Y1 is expressed in enteric smooth muscle cells and S100 in enteric glial cells. b In the myenteric plexus, P2Y2 is detected in neurons. c P2Y4 is detected in enteric glial cells. d P2Y6 is expressed in vascular and enteric smooth muscle cells. e P2Y11 is detected in enteric glial cells and P2Y12 is expressed in enteric nerves (f). Adapted from reference 30 with permission of Elsevier