DUODENAL BICARBONATE SECRETION AND MUCOSAL PROTECTION - NEUROHUMORAL INFLUENCE AND TRANSPORT MECHANISMS

Duodenal mucosal bicarbonate secretion (DMBS) plays an important role in the defence against acid discharged from the stomach. The secretion by duodenum immediately distal to the Brunner's glands area and devoi d of pancreatic and biliary secretions, was investigated in vivo in an aesthetized Sprague-Dawley rats and in vitro in mucosae isolated from the American bullfrog. Transport mechanisms were studied in isolated r at duodenal enterocytes and identified by use of digitized microfluoro metry and the fluoroprobe BCECF. Cyclic AMP production in enterocytes of villus vs. crypt origin was measured with radioimmunoassay. The ben zodiazepines diazepam and Ro 15-1788 stimulated DMBS in the rat when a dministered intravenously or intracerebroventricularly; however, their stimulatory effect was abolished by bilateral proximal vagotomy, and they had no effect on the secretion by isolated bullfrog mucosa. It is concluded that these benzodiazepines stimulate secretion by acting up on the central nervous system and that their effects are vagally media ted. Dopamine, the catechol-0-methyl-transferase-inhibitor nitecapone, and the dopamine D1 agonist SKF-38393 all stimulated DMBS. The periph erally acting antagonist domperidone while having no influence on basa l DMBS did prevent the influences of SKF-38393 and nitecapone. The alp ha1-antagonist prazosin had no such effects and the combined results s uggest that DMBS is stimulated via peripheral dopamine D1 receptors. I ntravenous, but not central nervous, administration of the muscarinic M1 receptor antagonists pirenzepine and telenzepine effectively stimul ated DMBS; however their effectiveness was dependent on intact vagal n erves. Phentolamine, an unselective alpha-adrenergic antagonist, preve nted the stimulation by pirenzepine and telenzepine and stimulation by carbachol was abolished by hexamethonium. It is concluded that periph eral nicotinergic and muscarinergic M1 receptors mediate stimulation o f DMBS, in part by acting upon peripheral sympathetic ganglia. Whereas dopamine and SKF-38393 caused a time-dependent increase in the accumu lation of cyclic AMP in duodenal enterocytes of crypt and villous orig in, the D2 agonist quinpirole had an inhibitive influence. Crypt and v illus cells differed in their respective time-courses in response to v asoactive intestinal polypeptide. Finally, Cl-/HCO3- exchange, Na+/Hexchange and NaHCO3 cotransport were identified as membrane acid/base transport mechanisms in isolated duodenal enterocytes.