Somatostatin is known to inhibit
hormone release and gastrointestinal secretion and hence may be useful in the treatment of
amine precursor uptake,
decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural
hormone. Our study evaluated the effect of a synthetic analog of
somatostatin,
SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated
gastrin release and gastric acid secretion in 10 patients with the
Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours;
SMS 201-995, 1 microgram/kg, was given subcutaneously;
gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline
gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a
secretin (2 U/kg) or a
calcium stimulation test (2 mg/kg) with or without pretreatment with
SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in
gastrin (ng X 60 min/ml) without
SMS 201-995, 36.8 +/- 11 (
secretin), and 129 +/- 30 (
calcium) were reduced with
SMS 201-995 to -1.1 +/- 0.76 (
secretin) and -29 +/- 28 (
calcium) (p less than 0.05). In the
Zollinger-Ellison syndrome,
SMS 201-995 caused significant and long-lasting inhibition of both
tumor gastrin release and gastric acid secretion, probably by direct action on both the
gastrinoma and the stomach.
SMS 201-995 blocks
acid secretion and
secretin- and
calcium-stimulated
gastrin release, indicating that
SMS 201-995 inhibits
peptide secretion by postreceptor mechanisms.
SMS 201-995 will be useful in the
palliative treatment of
apudomas.