BACKGROUND & AIMS: An extensive enteric distribution of GABAergic neurons and nerve fibers has been identified in a number of species, including humans, but the role of gamma-aminobutyric acid (GABA) in mucosal physiology is unclear. The study was designed to determine if GABA stimulates electrolyte transport in an in vitro guinea pig ileum model. METHODS: The localization of GABAergic innervation in the submucosa and mucosa was determined using autoradiography. The effects of GABA and its analogues on electrolyte transport were measured in stripped guinea pig ileum mounted in Ussing chambers. Sensory afferent-evoked secretion after GABAA receptor blockade was also assessed. RESULTS: GABA and the GABAA receptor agonist 3-amino-1-propanesulfonic acid, but not the GABAB agonist baclofen, caused a bicuculline- and tetrodotoxin-sensitive, biphasic increase in short-circuit current. The response to 3-amino-1-propanesulfonic acid was partially reduced by atropine, implicating cholinergic secretomotor neurons, and by the histamine H1 antagonist pyrilamine, suggesting the involvement of a histamine-releasing cell. The GABAA receptor antagonist bicuculline and 3-amino-1-propanesulfonic acid-induced tachyphylaxis, but not the GABAA-associated chloride channel blocker picrotoxinin, caused a modest reduction in the secretory responses to capsaicin. CONCLUSIONS: Activation of submucosal GABAA receptors elicits a multifactorial secretory response but plays a minor role in capsaicin-sensitive, afferent-evoked secretion.
BACKGROUND & AIMS: An extensive enteric distribution of GABAergic neurons and nerve fibers has been identified in a number of species, including humans, but the role of gamma-aminobutyric acid (GABA) in mucosal physiology is unclear. The study was designed to determine if GABA stimulates electrolyte transport in an in vitro guinea pig ileum model. METHODS: The localization of GABAergic innervation in the submucosa and mucosa was determined using autoradiography. The effects of GABA and its analogues on electrolyte transport were measured in stripped guinea pig ileum mounted in Ussing chambers. Sensory afferent-evoked secretion after GABAA receptor blockade was also assessed. RESULTS:GABA and the GABAA receptor agonist 3-amino-1-propanesulfonic acid, but not the GABAB agonist baclofen, caused a bicuculline- and tetrodotoxin-sensitive, biphasic increase in short-circuit current. The response to 3-amino-1-propanesulfonic acid was partially reduced by atropine, implicating cholinergic secretomotor neurons, and by the histamine H1 antagonist pyrilamine, suggesting the involvement of a histamine-releasing cell. The GABAA receptor antagonist bicuculline and 3-amino-1-propanesulfonic acid-induced tachyphylaxis, but not the GABAA-associated chloride channel blocker picrotoxinin, caused a modest reduction in the secretory responses to capsaicin. CONCLUSIONS: Activation of submucosal GABAA receptors elicits a multifactorial secretory response but plays a minor role in capsaicin-sensitive, afferent-evoked secretion.