Somatostatin Inhibition and Reversal of Parathyroid Hormone-, Calcium-, and Acetylcholine-Induced Gastrin Release in the Pig*

The ability of somatostatin (somatotropin release-inhibiting factor or SRIF) to inhibit or reverse an increased release of gastrin induced by infusion of CaCl2, parathyroid hormone (PTH), and acetylcholine (Ach) was examined in 21 young anesthetized pigs, weighing 15–25 kg. Test substances were administered (0.05–0.1 ml/min for 20 min) directly into the antral circulation via a catheter in the right gastroepiploic artery. Samples of venous blood draining the antrum were collected from a catheter in the right gastroepiploic vein, and gastrin was measured by RIA. The following results were obtained: 1) in six pigs, infusion of SRIF (synthetic ovine, 1.67–16.7 μg/min) consistently lowered basal gastrin in antral plasma (-73 ± 5%, P < 0.001 to < 0.05); 2) infusion of SRIF (1.67–16.7 μg/min) together with PTH (0.04–0.4 U/min) in five pigs prevented the 20- to 30-fold rise in gastrin observed after infusion of PTH alone (mean increase with PTH plus SRIF, +26%; with PTH alone, +2460%; P < 0.001 to < 0.01); 3) infusion of SRIF (1.67 μg/min) together with 0.05 M CaCl2 in five pigs markedly inhibited the large increase in gastrin release produced by CaCl2 alone (SRIF plus Ca, +713%; Ca alone, +8220%; P < 0.0025 to < 0.05); 4) infusion of SRIF (3.34–16.7 μg/min) together with 0.1 M Ach largely inhibited the 10- to 20-fold rise in gastrin observed after infusion of Ach alone in three of six pigs (SRIF plus Ach, +250%; Ach alone, +1420%; P < 0.05 to < 0.005 in three of six pigs); 5) infusion of SRIF (1.67–16.7 μg/min) after prior stimulation of gastrin secretion by PTH, CaCl2, or Ach produced a rapid and pronounced reversal in gastrin secretion (from stimulated levels: after PTH, -78%, P < 0.001 to < 0.05 in three pigs; after Ca, -79%, P < 0.025 in three of four pigs; after Ach, -86%, P < 0.001 to < 0.05 in five pigs). The results show that SRIF not only can inhibit gastrin release induced by PTH, Ca, and Ach, but also can largely reverse the hypergastrinemia caused by these diverse gastrin secretagogues.