After high or chronic alcohol intake, motility disorders of the gastrointestinal (GI) tract are particularly common, including decreased esophageal peristalsis, esophageal reflux, abnormal gastric emptying, hyperactive bowel and diarrhea. Although ethanol (EtOH) is generally assumed to act directly on GI smooth muscle, the P.I.'s preliminary studies suggest that a more sensitive target is the enteric nervous system (ENS) within the gut wall. The ENS coordinates the propulsion (peristalsis) of chyme throughout the GI tract. From their preliminary studies in the guinea-pig ileum the investigators have found EtOH to enhance enteric excitatory reflexes and peristalsis at low concentrations (0.001 to 0.2% v/v) by apparently increasing cholinergic and non-cholinergic neurotransmission, whereas, EtOH at higher concentrations (>0.5 % v/v), depresses both enteric excitatory reflexes and peristalsis by postsynaptic actions on myenteric neurons. In light of these observations, the long term aim of this study is to determine the actions of acute EtOH on neurotransmission in the guinea-pig ileum in-vitro. The guinea-pig ileum is an excellent model for these studies as a hierarchy of powerful and sensitive techniques have been developed for this tissue that will enable the effects of EtOH on enteric neurotransmission to be investigated at many levels, ranging from peristalsis in isolated segments of ileum down to the level of individual myenteric neurons. In particular, the P.I. will study the actions of EtOH on; i) peristalsis, ii) specific ascending excitatory and descending inhibitory nerve pathways to muscles that underlie peristalsis; iii) reflex responses in enteric neurons located in specific nerve pathways; and iv) membrane properties and synaptic inputs (fast and slow) of characterized myenteric neurons. As EtOH can effect the gut by direct actions on the mucosa, they will also test v) whether EtOH can effect peristalsis by directly stimulating intrinsic sensory nerve endings in mucosal villi, and vi) determine whether EtOH acts directly or indirectly on neural excitability by releasing neuromodulators such as nitric oxide, serotonin, opiodes, adenosine or prostaglandins. This study will provide significant insights into how EtOH affects enteric neurotransmission to alter gut motility.
