Cholinergic mechanisms involved in release and effect of prostaglandin E2 in HCI‐stimulated duodenal HCO‐3 secretion in the conscious rat

Using a proximal duodenal loop in conscious rats, we investigated interactions between prostaglandin E2 and nicotinic and muscarinic receptor mechanisms previously found to be involved in the duodenal HCO-3 response to HC1. In previous studies using the same model, a 5-min perfusion of the duodenal loop with 150 mmol 1-1 HC1 produced a marked and sustained HCO-3 response. In the present study, the identical challenge produced a rapid 20-fold increase in the luminal output of prostaglandin E2 during acid exposure, followed by a sustained more than twofold elevation above the basal level during the 45 min monitored. The prostaglandin synthesis inhibitor indomethacin (4 mg kg-1 i.p.) suppressed the output of prostaglandin E2 during the HC1 challenge from 131 ± 84 to 15.4 ± 10.0 pmol cm-1 h-1, and in the post-stimulatory period from 17.3 ± 9.1 to 4.4 ± 2.2 pmol cm-1 h-1. The nicotinic receptor antagonist hexamethonium (20 mg kg-1 i.v.) had no effect on the output of prostaglandin E2. The muscarinic receptor antagonist atropine (0.5 mg kg-1 s.c.) had no effect on the output of prostaglandin E2 during HC1 challenge, but reduced the post-stimulatory output to 7.7 4PL 4.1 pmol ch-1 h-1. Perfusion of the duodenal loop with 0.1 mmol 1-1 prostaglandin E2 produced a HCO-3 response that was abolished by hexamethonium (20 mg kg-1 i.v.), but not affected by atropine (0.5 mg kg-1 s.c). The results indicate that muscarinic receptor mechanisms are involved in the HCI-stimulated local formation of prostaglandin E2 and that nicotinic receptor mechanisms are required for the duodenal HCO-3 secretion stimulated by prostaglandin E2.