A gastric factor, calcitonin, and the hypocalcemia induced by gastrointestinal hormones.

Abstract

To clarify the mechanism by which gastrointestinal peptides influence calcium homeostasis, we studied 1) the effect of pentagastrin (PG) on serum Ca and serum immunoreactive calcitonin (iCT) concentrations and 2) the effect of gastric acid inhibitors on PG- and histamine-induced hypocalcemia. Fasted male Holtzman rats (80–100 g) were used in groups of five to eight. In sham-operated rats (laparotomy), PG (25μg, iv) resulted in a rise of serum iCT from a basal value of 39 ± 5 pg/ml (mean ± SE) to a peak value of 60 ± 10 pg/ml (P < 0.05) at 2 min after injection. In these animals, the serum Ca decreased from a basal concentration of 10.2 ± 0.17 to 8.3 ± 0.15 mg/dl (P < 0.001) 30 min after the injection. In gastrectomized, thyroidintact animals, serum iCT increased from 31 ± 3 pg/ml to a peak value of 59 ± 9 pg/ml 5 min after PG (P < 0.01), a response which did not differ significantly from that of sham-operated rats. Despite this, serum Ca did not decrease from basal values at 30 min in gastrectomized animals. Finally, in acutely thyroparathyroidectomized rats, iCT values were undetectable at all times. However, Ca decreased from 9.1 ± 0.23 to 8.0 ± 0.17 mg/ dl 30 min after PG (P < 0.005) in these animals. In studies related to the effect of inhibitors of gastric acid secretion, the administration of PG alone in sham-operated animals was followed by a Ca decrease of 2.1 mg/dl or greater. However, this PG-induced hypocalcemia was completely in inhibited by atropine (4 μg), secretin (1U), or metiamide (0.12 mg) when these agents were administered with PG. None of these gastric acid inhibitors influenced Ca when given alone. The administration of histamine base (1.0 mg) was followed by a similar decrease in Ca of 1.7 mg/dl or greater 30 min after its injection. The injection of either atropine (2 μg) or metiamide (0.48 mg) completely inhibited all hypocalcemia resulting from the histamine. However, secretin in doses as large as 10 U had no inhibitory effect on the lowering of serum calcium by histamine. Finally, transabdominal vagotomy significantly reduced the Ca-lowering activity of both PG and histamine. These studies clearly demonstrate that PG in pharmacological doses is a CT secretagogue in the rat, although not a potent one. However, the decrease of Ca after PG appears to be independent of hypercalcitoninemia and only occurs when an intact stomach is present. Furthermore, the findings that 1) atropine and metiamide abolish all PG- and histamine-induced hypocalcemia, 2) secretin blocks PG- but not histamine-induced hypocalcemia, and 3) transabdominal vagotomy decreases the hypocalcemia after both PG and histamine administration strongly suggest that a gastric factor related to acid secretion plays the most important role in mediating the influence of these gastrointestinal factors on serum calcium levels in the rat.