Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs.
The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- output from the isolated, perfused (24 mM NaHCO3 + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E2 (PGE2). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO3- secretion (3.5 +/- 0.2 mumol/cm/10 min) was reduced dose dependently by somatostatin-14 (10(-11) mol/kg, 10(-9) mol/kg, and 10(-7) mol/kg). Carbachol, VIP, and PGE2 (all 10(-8) mol/kg) increased basal duodenal HCO3- secretion two- to threefold. Somatostatin-14 (10(-7) mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE2. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4 +/- 1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10(-6) mol/liter) or carbachol (10(-3) mol/liter). VIP (10(-8) mol/liter) and PGE2 (10(-7) mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10(-6) mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.
Odes
H S
HS
Institute of Gastroenterology, Soroka Medical Center, Beer Sheva, Israel.
Muallem
R
R
Reimer
R
R
Ioffe
S
S
Beil
W
W
Schwenk
M
M
Sewing
K F
KF
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007419:Intestinal Secretions / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001639:Bicarbonates; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D002217:Carbachol; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007213:Indomethacin