INFLUENCE OF CA2-TERMINAL IPTH IN PENTOBARBITAL-ANESTHETIZED DOGS( CONCENTRATION ON THE CLEARANCE AND CIRCULATING LEVELS OF INTACT AND CARBOXY)

The role of hormone secretion and hormone clearance in the differentia l control of circulating levels of intact (I-) and carboxy-terminal (C -) immunoreactive parathyroid hormone (iPTH) was evaluated in 18 pento barbital-anesthetized dogs, Catheters were installed in the aorta, lef t renal, and hepatic veins for sampling. Hepatic and renal blood flows were calculated from sulfobromophtalein (BSP) and p-aminohippuric aci d (PAH) extraction and clearance, I- and C-iPTH were measured during a 1 h of infusion of CaCl2 or Na(2)EDTA. High-performance liquid chroma tography (HPLC) profiles of I- and C-iPTH in and out of tile liver and kidney were also obtained. Data on two dogs (one CaCl2 and one Na(2)E DTA infusion) were pooled for the analysis of one parathyroid function using a four-parameter mathematical model. Results obtained in the ba sal state and during analysis of the parathyroid function were also co mpared with those of 24 awakened dogs. Results are means +/- SD. Anest hetized dogs had lower levels of Ca2+ (1.29 +/- 0.03 vs. 1.34 +/- 0.04 mmol/l; p < 0.001) and higher levels of I- (11.5 +/- 5.7 vs, 3.0 +/- 1.9 pmol/l, p < 0.001) and C-iPTH (52 +/- 20.9 vs. 22.8 +/- 10.5 pmol/ l; p < 0.001) than awakened dogs. Their stimulated (S) and nonsuppress ible (NS) I-iPTH levels were increased 2- and 4-fold, respectively, wh ile similar C-iPTH levels rose only 1.35- and 1.75-fold; this caused t heir S (4.4 +/- 0.7 vs. 6.8 +/- 1.9; p < 0.001) and NS (24.6 +/- 11.8 vs. 49.8 +/- 27.5; p < 0.05) C-iPTH/I-iPTH ratios to decrease. This wa s not explained by different renal clearance rates of I- and C-iPTH si nce both were similar at similar to 10 ml/kg/minute and unaffected by Ca2+ concentration. Clearance of all I- and C-iPTH HPLC molecular form s by the kidney appeared equal, A 50% decrease in the hepatic clearanc e of I-iPTH to similar to 12 ml/kg/minute in pentobarbital-anesthetize d dogs, related to a lower hepatic blood flow, explained the higher le vels of S and NS I-iPTH in these animals, I-iPTH hepatic clearance was unaffected by Ca2+ concentration. C-iPTH hepatic clearance was much l ower at similar to 5 ml/kg/minute, abolished by hypercalcemia, and red uced by the influence of anesthesia on hepatic blood now. This also ex plained the higher S C-iPTH levels in anesthetized animals. I-PTH(1-84 ) detected by the C-iPTH assay explained only 37.6% of the hepatic C-i PTH clearance in hypocalcemia and 73.3% in hypercalcemia. Overall, our results indicate that total C-iPTH clearance is about 40.2% that of I -iPTH in hypocalcemia and 41.3% in hypercalcemia, This would only expl ain a 2.4- to 2.5-fold difference in circulating levels of I- and C-iP TH if secretion rates were equal; the larger difference observed in S and NS C-iPTH/I-iPTH ratio values is thus mainly explained by differen t production rates.