GAMMA-AMINOBUTYRIC-ACID STIMULATES ELECTROLYTE TRANSPORT IN THE GUINEA-PIG ILEUM IN-VITRO

Background & Aims: An extensive enteric distribution of GABAergic neur ons and nerve fibers has been identified in a number of species, inclu ding humans, but the role of gamma-aminobutyric acid (GABA) in mucosal physiology is unclear. The study was designed to determine if GABA st imulates electrolyte transport in an in vitro guinea pig ileum model. Methods: The localization of GABAergic innervation in the submucosa an d mucosa was determined using autoradiography. The effects of GABA and its analogues on electrolyte transport were measured in stripped guin ea pig ileum mounted in Ussing chambers. Sensory afferent-evoked secre tion after GABA(A) receptor blockade was also assessed. Results: GABA and the GABA(A) receptor agonist 3-amino-1-propanesulfonic acid, but n ot the GABA(B) agonist baclofen, caused a bicuculline and tetrodotoxin -sensitive, biphasic increase in short-circuit current. The response t o 3-amino-1-propanesulfonic acid was partially reduced by atropine, im plicating cholinergic secretomotor neurons, and by the histamine H-1 a ntagonist pyrilamine, suggesting the involvement of a histamine-releas ing cell. The GABA(A) receptor antagonist bicuculline and 3-amino-1-pr opanesulfonic acid-induced tachyphylaxis, but not the GABA(A)-associat ed chloride channel blocker picrotoxinin, caused a modest reduction in the secretory responses to capsaicin. Conclusions: Activation of subm ucosal GABA(A) receptors elicits a multifactorial secretory response b ut plays a minor role in capsaicin-sensitive, afferent-evoked secretio n.