BICARBONATE SECRETION IN THE GUINEA-PIG DUODENUM - FUNCTIONAL-CHARACTERIZATION OF PEPTIDE-HORMONE RECEPTORS IN DUODENAL ENTEROCYTES

To get information about the peptide hormone receptors involved in duo denal bicarbonate secretion (DBS) and their cellular location, we dete rmined DBS and adenylate cyclase (AC) activity in response to hormones of the vasoactive intestinal polypeptide (VIP)/secretin family of pep tides. DBS was determined in an isolated, perfused (24 mmol/l NaHCO3) loop of the proximal duodenum in urethane- and indometacin-treated gui nea pigs. AC stimulation was measured in isolated, homogenized duodena l enterocytes, the histological evaluation of which revealed their vil lous origin. VIP (10(-9) to l0(-7) mol x kg(-1)) dose-dependently incr eased DBS 3.5-fold (p < 0.01); this effect was completely inhibited by the VIP antagonist [D-p-C1-Phe6,Leu17]VIP (10(-6) mol x kg(-1)). Gluc agon (10(-8) to 10(-6) mol x kg(-1)) increased DBS 2.1-fold, while sec retin (10(-9) to 10(-6) mol x kg(-1)) had no effect on DBS, but stimul ated pancreatic bicarbonate secretion. VIP concentration-dependently i ncreased AC activity 5.6-fold with an EC(50) of 1.3 x 10(-9) mol/l. [D -p-C1-Phe6,Leu17]VIP caused a rightward shift of the VIP concentration -response curve. A Schild plot analysis yielded a slope of 0.85 +/- 0. 11, indicating competitive inhibition. While secretin also stimulated AC activity, although 1,000-fold less potent than VIP, glucagon was in effective. These data indicate that specific VIP receptors, which medi ate VIP-stimulated bicarbonate secretion, are present on villous enter ocytes. Stimulation of AC by secretin seems to be of pharmacological r elevance only and is consistent with the lack of effect of this hormon e on DBS. Glucagon likely activates a second transmitter of bicarbonat e secretion, or works independently of AC.