Cholinergic mechanisms involved in release and effect of prostaglandin E2in HCI-stimulated duodenal HCO-3secretion in the conscious rat

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Abstract
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 HCO3- response to HCl. In previous studies using the same model, a 5-min perfusion of the duodenal loop with 150 mmol l-1 HCl produced a marked and sustained HCO3- 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 HCl challenge from 131.+-.84 to 15.4.+-.10.0 pmol cm-1 h-1, and in the post-stimulatory period from 17.cntdot.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 anatagonist atropine (0.5 mg kg-1 s.c.) had no effect on the output of prostaglandin E2 during HCl challenge, but reduced the post-stimulatory output to 7.7.+-.4.1 pmol cm-1 h-1. Perfusion of the duodenal loop with 0.1 mmol l-1 prostaglandin E2 produced a HCO3- 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 HCl-stimulated local formation of prostaglandin E2 and that nicotinic receptor mechanisms are required for the duodenal HCO3- secretion stimulated by prostaglandin E2.