Hypocalcemic Effect of Pentagastrin and Related Gasitrointestinal Hormonal Peptides in the Rat1

Abstract

The hypocalcemic effect of gastrointestinal hormonal peptides was evaluated in young fasted rats. Systemic iv injection of synthetic pentagastrin and tetragastrin and of native porcine gastrin in doses of 4-12 μg/rat produced modest hypocalcemia (fall of 6-12%) IS and 30 min later. By 60 min after injection normocalcemia was reestablished. Single injections of pentagastrin produced hypophosphatemia as well as hypocalcemia. The hypocalcemic effect of pentagrastrin was abolished after acute removal of the thyroid gland, suggesting that the secretion of thyrocalcitonin (TCT) was involved. This interpretation also was supported by the fact that the magnitude and duration of hypocalcemia produced in rats by iv gastrointestinal peptides could be mimicked by a small (0.25 mU) iv dose of porcine TCT. In related experiments, multiple iv injections of pentagastrin at 30-min intervals into intact rats failed to maintain the hypocalcemic effect observed 30 min after a single injection. Injection of a high dose of betazole, the analog of histamine which stimulates gastric acid secretion independently of gastrin, failed to produce hypocalcemia or hypophosphatemia. This finding suggests that the effects of gastrointestinal hormonal peptides on serum calcium and phosphorus probably were not mediated by stimulation of gastric acid production per se. The present findings in the rat, along with our earlier results in the pig, indicate that the action of gastrin and gastrin—like peptides to promote TCT secretion is not a unique effect demonstrable in only one species, and the results are in line with our earlier hypothesis that gastrin or a related gastrointestinal hormonal peptide may be involved in the physiological regulation of secretion of TCT. (Endocrinology91: 1455, 1972)