The rapid effects of parathyroid hormones and a variety of prostaglandins on net uptake of 45Ca into the skeleton have been investigated in chicks and, in a limited parallel study, in immature rats. Intravenous injection of bovine (b) parathyroid hormone(1-34) (bPTH(1-34)) or 16,16-dimethyl prostaglandin E2 (16,16-dimethyl PGE2) in a 45Ca-labelled vehicle, combined with subsequent microwave fixation of tissue isotope levels, resulted in rapid (3-15 min) net inhibition of 45Ca uptake into endochondral bone (femur) in chicks (12 days old) and rats (4 weeks old). Use of 125I-labelled albumin and [14C]mannitol indicated that these responses were not a reflection of gross changes in tissue vascular or extracellular space. In rats, bPTH(1-84) also caused significant net inhibition of 45Ca uptake into femur at 10 min. Both bPTH(1-34) and 16,16-dimethyl PGE2 produced generally smaller decreases in 45Ca uptake into chick dermal bone (calvarium) at 3-15 min. In rat calvarium, however, these agents stimulated net uptake of 45Ca at these times. When microwave fixation was omitted, inhibitory responses were reduced or disappeared, while the stimulatory response in rat calvarium was enhanced. Responses to natural prostaglandins (PGE1, PGE2, PGF2 alpha and PGI2) in chicks at 3 min were similar but less marked than those to 16,16-dimethyl PGE2; 45Ca uptake into femur and, to a lesser extent in calvarium, being inhibited. In rats, PGE1, PGE2 and PGF2 alpha showed a tendency to decrease 45Ca uptake into femur while PGE1 and PGE2 both increased 45Ca uptake into calvarium.

Mechanisms of initial hypercalcaemic responses to parathyroid hormone (PTH) and 16,16-dimethyl prostaglandin (PG) E2 have been investigated in 10-to 12-day-old chicks in vivo using a combination of acute 45Ca injection and microwave fixation to stabilize tissue isotope levels. Single i.v. injection of 16,16-dimethyl PGE2 (20 micrograms/100 g body wt) caused an approximately 100% increase in soft tissue 45Ca levels compared with vehicle control injected chicks at 30 min. 45Ca levels were lowered in calvarium by 26% and in femur by 60% with this treatment. Bovine PTH (1-34) (3.3 micrograms/100 g body wt) had no effect on soft tissue 45Ca levels, but in calvarium it had a similar effect to the PG. In femur this dose of PTH lowered 45Ca by 19%. When expressed on an absolute basis (c.p.m./100 mg tissue wt), responses to the PG in soft tissue were only 3 and 10% respectively of those in femur and calvarium. The duration of inhibitory responses in bone were examined and those to PTH found to be transient (less than 45 min) compared with the responses to the PG (greater than 135 min). Dose-response curves for PTH- and PG-induced inhibition of 45Ca uptake into femur at 15 min were essentially parallel and indicated that the lowest doses of PTH and PG used (0.74 micrograms and 1.1 micrograms/100 body wt respectively) produced significant responses. In a separate experiment it was found that inhibition of 45Ca uptake into femur was evident as early as 3 min following PTH or PG injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Two human parathyroid hormone-related protein (hPTHrP) fragments were tested for effects on maternofetal transfer of 45Ca and Mg across the in-situ perfused rat placenta at 21 days of gestation (term = 23 days). The fetal placental circulation was perfused with a Mg-free Krebs-Ringer solution and the unidirectional maternofetal clearance (Kmf) of 45Ca and Mg compared with that of 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with hPTHrP(1-34) (100 ng/ml) or hPTHrP(75-86)amide (50 ng/ml) did not significantly alter the Kmf of 45Ca or that of Mg. In separate rats, however, hPTHrP(1-34) but not hPTHrP(75-86)amide stimulated marked placental cyclic AMP (cAMP) release, the peak response of 63 +/- 7 pmol/min occurring 10 min after the beginning of the peptide perfusion. A lower dose of hPTHrP(1-34) (4 ng/ml) produced a similar peak release of cAMP, as did [Nle8,21, Tyr34]-rPTH(1-34)amide (4 ng/ml) and the adenylate cyclase agonist forskolin (17 mumol/l). Forskolin also rapidly increased the Kmf of 45Ca but not that of Mg or 51Cr-EDTA. The present study indicates that hPTHrP does not acutely affect maternofetal transfer of Ca or Mg across the perfused rat placenta. The data also question the role played by cAMP in the stimulatory actions of forskolin on placental Ca transport.

ABSTRACT. Mechanisms of maternofetal Mg transfer gradient does not reflect greater protein binding in fetal plasma, have been investigated across the in situ perfused rat ultrafiltrable Mg concentrations also being higher in fetal complacenta at 21 d gestation (term = 23 d). The fetal placental pared with maternal plasma (1). These observations indicate that circulation was perfused with Mg-free Krebs-Ringer solu-placental transfer of Mg from mother to fetus must occur against tion and clearance of Mg from maternal plasma across the a chemical gradient. Using '*Mg, Care et al. (4) determined placenta [unidirectional maternofetal clearance (K,3 Mg] maternofetal and fetomaternal Mg fluxes of 0.042 and 0.012 compared with that for 4sCa and "Cr-EDTA, the latter mg. h-I. kg-' fetus, respectively, in sheep at 13 d preterm. These being used as a diffusional marker. Because diffusion coef-fluxes suggest the presence of an active mechanism for the ficients determined for these solutes were similar (6.8-7.6 maternofetal transfer of Mg. x cm2.sec-I), greater Kmf values determined for Mg In our study, maternal and fetal plasma Mg concentrations and 45Ca (mean f SD: 26.7 f 9.2 and 93.1 f 29.8 pL. (total and ultrafiltrable) were measured in the near term rat and min-' .g-' placenta, respectively) compared to "Cr-EDTA maternofetal Mg transfer was investigated using the in situ (um-(3.2 f 0.9 pL . min-' . g-I) suggest that maternofetal trans-bilically) perfused rat placenta preparation (7). K,f of 24Mg was fer of these cations occurs by mechanisms in addition to compared with that of "Cr-EDTA, used as a diffusional marker diffusion. Kmf Mg was also greater than Kmf "Cr-EDTA (7), and also with that of 45Ca, a divalent cation with which Mg when measured across the dually perfused rat placenta, in may share transcellular transport systems (8). Previous studies which the maternal uterine artery was additionally perfused (9) suggest that Ca is actively transferred across the in situ with Mg-containing (0.5 mmol. L-') Krebs-Ringer solu-perfused rat placenta. The effects of adding KCN to the perfusion tion. Decreasing the Mg concentration in the maternal fluid or decreasing perfusate temperature were therefore examperfusate by 90% reduced Mg appearance in the fetal ined for effects on possible active placental transfer of Mg as well perfusate by 87% within 8 min; this suggests that Kmf Mg as of 45Ca. Experiments were also performed using a dually across the in situ perfused placenta largely reflects Mg perfused rat placenta in which the maternal uterine artery was transfer from maternal plasma and not simply elution of a additionally perfused with Krebs Ringer solution with or without placental Mg pool. Addition of KCN (1 mrno1.L-I) to the Mg (10). These were performed to confirm that Mg transfer (as fetal perfusate or lowering perfusate temperature from 37 measured using the in situ perfused placenta) reflects maternoto 26°C significantly reduced Kmf Mg and Kmf 45Ca across fetal transfer and not simply elution of a placental Mg poo...