Abstract

Pancreatic secretion is regulated by the dorsal vagal nucleus (DVN) which is modulated by several neurotransmitters and diverse synaptic inputs. The inhibitory neurotransmitter GABA is a major modulator of the vagal output to the gastrointestinal tract. The present study investigated the effects of GABA(A) receptor blockade in the DVN, using bicuculline methiodide (BIM, GABA(A) receptor antagonist, 100 pmol/25 nl), on pancreatic exocrine secretion (PES). Male Sprague-Dawley rats anaesthetised with isoflurane were used in all experiments. PES was collected from the common bile-pancreatic duct and was used to determine the pancreatic protein output (PPO). PES and PPO were measured prior to, and after, microinjection of BIM into the DVN. Bilateral microinjection of BIM into the DVN significantly increased PES and PPO from 23.4+/-3.2 microl/h to 66.1+/-17.5 microl/h and 19.3+/-1.7 microg/h to 35.7+/-3.0 microg/h (P<0.05), respectively. Atropine methonitrate (100 microg/(kg min), i.v.) blocked the excitatory effect of BIM microinjection on PES and PPO. These results suggest that activation of DVN neurons stimulates pancreatic secretion via a cholinergic muscarinic mechanism.

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