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Bombesin was administered to young fasted rats, and blood levels of immunoreactive gastrin and calcitonin (CT) were measured. Doses of bombesin up to 100 μg/rat i.v. did not affect serum calcium or phosphorus. Five minutes after bombesin, 10 or 50 μg/rat, serum gastrin increased 1- to 2-fold and, by 30 min, it was elevated 5- to 10-fold. Time-course and dose-response studies showed that doses of 10–100 μg/rat increased gastrin and that gastrin rose within 5 min after 50 μg/rat and remained elevated for at least 2 hr. Despite bombesin-induced hyper-gastrinemia, CT remained low or undetectable (<50–100 pg/ml) at all times. In one study, somatostatin (50 μg/rat i.v.), given together with bombesin, inhibited the rise in serum gastrin by 50%, but serum CT, which was detectable, was unaffected by either bombesin or somatostatin. We conclude that bombesin stimulates gastrin release in the rat, but the elevated gastrin does not promote CT secretion. The results support our earlier findings which indicate that gastrin is weak or ineffective in the rat as a CT secretagogue.The technical assistance of Ms. Deloris B. Alston and Ms. Lillie T. Williams is gratefully acknowledged.

Previously we reported a homologous radioimmunoassay for rat thyrocalcitonin (TCT) which was sensitive enough (2-3 ng/ml serum) to measure TCT in thyroid venous blood or thyroid gland extracts but could not detect TCT in peripheral blood even after provocative challenge with iv calcium. In the present study chicken antisera to rat TCT were developed which were sufficiently sensitive (120-240 pg/ml serum) to permit initial evaluation of changes in TCT in rat peripheral blood. The following results were observed: (1) Basal serum TCT in young male Holtzman rats was undetectable, being < 120-240 pg/ml; (2) induction of marked hypercalcemia by iv calcium increased TCT to ∼1000-3000 pg/ml within 5 min; (3) thyroid cautery increased TCT to ∼1000 pg/ml in 5-15 min; (4) calcium gavage (12.2 mg Ca/100 g) produced modest hypercalcemia in 30-60 min and increased serum TCT to ∼500 pg/ml; (5) injection of isoproterenol raised serum TCT detectably; (6) injection of large doses of gastrin or pentagastrin did not produce detectable increases in TCT 5 or 30 min later.The results show that suitable antisera to rat TCT can be developed in chickens and applied to the measurement, by radioimmunoassay, of elevated circulating levels of TCT in the rat.The authors wish to acknowledge advice from Drs. Paul L. Munson and Tai-Chan Peng, and technical assistance from Mrs. Deloris B. Alston and Mr. John R. Hagaman, Jr.

Previously we found that adult Zucker fatty rats have C-cell hyperplasia and increased thyroidal calcitonin (CT) compared to lean controls. In this study we have evaluated both secretion of CT and responsiveness to CT in order to see whether they, too, were altered. Fat rats and lean littermates, 13-15 months old, were used. CT secretion was provoked by (1) feeding for 2 hr after an 18-hr fast, (2) giving pentagastrin iv, and (3) injecting CaCl2iv. CT was measured by radioimmunoassay. Responsiveness to CT was examined by giving porcine or salmon CT iv and measuring serum Ca 1-3 hr later. For CT secretion, compared to leans the fat rats showed (1) higher fasting serum Ca and CT and a greater rise in CT after feeding, (2) a similar 5- to 10-fold increase in CT after iv pentagastrin, and (3) a greater rise in both serum Ca and CT at various times between 5 min and 3 hr after iv CaCl2. For CT responsiveness, fat and lean rats were equally responsive to iv CT in terms of the fall in plasma Ca 1-3 hr later. The results show that fat rats can secrete as much or more CT in response to provocative stimuli as lean rats and that they appear normally responsive to injected CT. Therefore, inability to release CT and insensitivity to CT do not underly the C-cell hyperplasia, increased thyroidal CT, and increased circulating CT in the fat rat.

Baby rats, 15 days old, were fasted > 13 hr and given 1.5 ml 5% glucose by stomach tube. Control babies were gavaged with 1.5 ml 0.9% NaCl which itself did not affect serum calcium or CT.Gavage with glucose produced a fall in serum calcium of 0.5-1.0 mg/dl 60 min later (P< 0.05-<0.005). Glucose produced a fall in serum phosphorus at 60 min similar to that in serum calcium. Measurement of immunoreactive CT in serum showed a significant rise from ~120 pg/ml or less up to as much as 900 pg/ml (P< 0.01). A time course study showed that serum CT increased and serum calcium decreased only at 60 min after oral glucose; values had not changed at 30 min and had returned to control levels by 90 min. In contrast, serum glucose was high (~300 mg/dl) at 30 min after gavage and had returned toward the control level (~130 mg/dl) by 60-90 min. The decrease in Ca after glucose must, at least in part, be due to CT since after thyroidectomy glucose did not produce a significant fall in serum calcium.The findings show that oral administration of a calcium-free solution can increase CT release in the absence of a rise in blood calcium.