γ-Aminobutyric acid stimulates electrolyte transport in the guinea pig ileum in vitro

Abstract

Background and 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 γ-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 GABA(A) receptor blockade was also assessed. Results: GABA and the GABA(A) receptor agonist 3- amino-1-propanesulfonic acid, but not the GABA(B) 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 GABA(A) receptor antagonist bicuculline and 3- amino-1-propanesulfonic acid-induced tachyphylaxis, but not the GABA(A)- associated chloride channel blocker picrotoxinin, caused a modest reduction in the secretory responses to capsaicin. Conclusions: Activation of submucosal GABA(A) receptors elicits a multifactorial secretory response but plays a minor role in capsaicin-sensitive, afferent-evoked secretion.