Background Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man. Methods We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD. Results In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1±7.0% and 63.9±6.5% (p<0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r=0.72, p=0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9±6.5% and 52.7±5.0%, (p<0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus. Conclusions Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.

Alterations in colonic motility are implicated in the pathophysiology of bowel disorders, but high-resolution manometry of human colonic motor function has revealed that our knowledge of normal motor patterns is limited. Furthermore, various terminologies and definitions have been used to describe colonic motor patterns in children, adults and animals. An example is the distinction between the high-amplitude propagating contractions in humans and giant contractions in animals. Harmonized terminology and definitions are required that are applicable to the study of colonic motility performed by basic scientists and clinicians, as well as adult and paediatric gastroenterologists. As clinical studies increasingly require adequate animal models to develop and test new therapies, there is a need for rational use of terminology to describe those motor patterns that are equivalent between animals and humans. This Consensus Statement provides the first harmonized interpretation of commonly used terminology to describe colonic motor function and delineates possible similarities between motor patterns observed in animal models and humans in vitro (ex vivo) and in vivo. The consolidated terminology can be an impetus for new research that will considerably improve our understanding of colonic motor function and will facilitate the development and testing of new therapies for colonic motility disorders.

Indirect evidence suggests that ATP is a neurotransmitter involved in inhibitory pathways in the neuromuscular junction in the gastrointestinal tract. The aim of this study was to characterize purinergic inhibitory neuromuscular transmission in the human colon. Tissue was obtained from colon resections for neoplasm. Muscle bath, microelectrode experiments, and immunohistochemical techniques were performed. 2′-deoxy- N⁶-methyl adenosine 3′,5′-diphosphate tetraammonium salt (MRS 2179) was used as a selective inhibitor of P2Y₁receptors. We found that 1) ATP (1 mM) and adenosine 5′-β-2-thiodiphosphate (ADPβS) (10 μM), a preferential P2Y agonist, inhibited spontaneous motility and caused smooth muscle hyperpolarization (about −12 mV); 2) MRS 2179 (10 μM) and apamin (1 μM) significantly reduced these effects; 3) both the fast component of the inhibitory junction potential (IJP) and the nonnitrergic relaxation induced by electrical field stimulation were dose dependently inhibited (IC₅₀∼1 μM) by MRS 2179; 4) ADPβS reduced the IJP probably by a desensitization mechanism; 5) apamin (1 μM) reduced the fast component of the IJP (by 30–40%) and the inhibitory effect induced by electrical field stimulation; and 6) P2Y₁receptors were localized in smooth muscle cells as well as in enteric neurons. These results show that ATP or a related purine is released by enteric inhibitory motoneurons, causing a fast hyperpolarization and smooth muscle relaxation. The high sensitivity of MRS 2179 has revealed, for the first time in the human gastrointestinal tract, that a P2Y₁receptor present in smooth muscle probably mediates this mechanism through a pathway that partially involves apamin-sensitive calcium-activated potassium channels. P2Y₁receptors can be an important pharmacological target to modulate smooth muscle excitability.

Abstract  Hydrogen sulphide (H₂S) has been recently proposed as a transmitter in the brain and peripheral tissues. Its role in the gastrointestinal tract is still unknown despite some data which suggest an involvement mediating smooth muscle relaxation. The aim of this study was to investigate the effect of this gas on intestinal segments from mouse jejunum and colon, and muscular strips from the human and rat colon. In isolated segments of mouse colon and jejunum, bath applied sodium hydrogen sulphide (NaHS) (a H₂S donor) caused a concentration‐dependent inhibition of spontaneous motor complexes (MCs) (IC₅₀ 121 μmol L⁻¹ in the colon and 150 μmol L⁻¹ in the jejunum). This inhibitory effect of NaHS on MCs was (i) unaffected by tetrodotoxin (TTX), capsaicin, pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonate and N‐nitro‐l‐arginine suggesting a non‐neural effect and (ii) significantly reduced by apamin 3 μmol L⁻¹. NaHS concentration‐dependently inhibited the spontaneous motility in strips from human colon (IC₅₀ 261 μmol L⁻¹) and rat colon (IC₅₀ 31 μmol L⁻¹). The inhibitory effect of NaHS on colonic strips was (i) unaffected by the neural blocker TTX (1 μmol L⁻¹) with IC₅₀ 183 μmol L⁻¹ for the human colon and of 26 μmol L⁻¹ for the rat colon and (ii) significantly reduced by glybenclamide (10 μmol L⁻¹), apamin (3 μmol L⁻¹) and TEA (10 mmol L⁻¹) with IC₅₀ values of 2464, 1307 and 2421 μmol L⁻¹ for human strips, and 80, 167 and 674 μmol L⁻¹ for rat strips respectively. We conclude that H₂S strongly inhibits in vitro intestinal and colonic motor patterns. This effect appears to be critically dependent on K channels particularly apamin‐sensitive SK channels and glybenclamide‐sensitive K (ATP) channels.

Normal motility of the colon is critical for quality of life and efforts to normalize abnormal colon function have had limited success. A better understanding of control systems of colonic motility is therefore essential. We report here a hypothesis with supporting experimental data to explain the origin of rhythmic propulsive colonic motor activity induced by general distention. The theory holds that both networks of interstitial cells of Cajal (ICC), those associated with the submuscular plexus (ICC-SMP) and those associated with the myenteric plexus (ICC-MP), orchestrate propagating contractions as pacemaker cells in concert with the enteric nervous system (ENS). ICC-SMP generate an omnipresent slow wave activity that causes propagating but non-propulsive contractions ("rhythmic propagating ripples") enhancing absorption. The ICC-MP generate stimulus-dependent cyclic depolarizations propagating anally and directing propulsive activity ("rhythmic propulsive motor complexes"). The ENS is not essential for both rhythmic motor patterns since distention and pharmacological means can produce the motor patterns after blocking neural activity, but it supplies the primary stimulus in vivo. Supporting data come from studies on segments of the rat colon, simultaneously measuring motility through spatiotemporal mapping of video recordings, intraluminal pressure, and outflow measurements.

Intracellular microelectrodes and organ bath techniques were used to study spontaneous cyclic electrical and mechanical activity in the rat colon. Electron microscopy and immunohistochemical studies showed two major populations of interstitial cells of Cajal (ICC): one associated with Auerbach's plexus (ICC-AP) and one with the submuscular plexus (ICC-SMP). The ICC-SMP network partly adhered to the submucosa when removed and was generally strongly damaged after separation of musculature and submucosa. Similarly, longitudinal muscle removal severely damaged AP. Two electrical and mechanical activity patterns were recorded: pattern A, low-frequency (0.5–1.5 cycles/min), high-amplitude oscillations; andpattern B, high-frequency (13–15 cycles/min), low-amplitude oscillations. Pattern A was recorded in preparations with intact AP but absent in those without intact AP.Pattern B was recorded in preparations with intact SMP but was absent in those lacking SMP. With full-thickness strips, the superimposed patterns A and B were recorded in circular muscle. When longitudinal muscle mechanical activity was recorded, only pattern A was present. We conclude that two pacemakers regulate rat colonic cyclic activity: the ICC-SMP network (responsible for cyclic slow waves and small-amplitude contractions) and the ICC-AP network (which may drive the cyclic depolarizations responsible for high-amplitude contractions). This is the first report showing consistent slow wave activity in the rodent colon.