Calcitonin (rat)

In this study we analyzed the response of parafollicular cells in rat thyroid gland after exposure to radiofrequency at 2.45 GHz using a subthermal experimental diathermy model. Forty-two Sprague Dawley rats, divided into two groups of 21 rats each, were individually exposed at 0 (control), 3 or 12 W in a Gigahertz Transverse Electro-Magnetic (GTEM) chamber for 30 min. After radiation, we used simple or fluorescence immunohistochemistry to measure calcitonin cells or cellular stress levels, indicated by the presence hyperplasia of parafollicular cells, heat shock protein (HSP) 90. Immunomarking of calcitonin-positive cells was statistically significant higher in the thyroid tissue of rats exposed to 2.45 GHz radiofrequency and cell hyperplasia appeared 90 min after radiation at the SAR levels studied. At the same time, co-localized expression of HSP-90 and calcitonin in parafollicular cells was statistically significant attenuated 90 min after radiation and remained statistically significantly low 24 h after radiation, even though parafollicular cell levels normalized. These facts indicate that subthermal radiofrequency (RF) at 2.45 GHz constitutes a negative external stress stimulus that alters the activity and homeostasis of parafollicular cells in the rat thyroid gland. However, further research is needed to determine if there is toxic action in human C cells.

1. We studied the absorption of human calcitonin across the colon of juvenile female rats in vivo. Both pharmacokinetic and pharmacodynamic parameters were monitored to measure absorption. 2. Intracolonically administered human calcitonin at doses of 0.1-5.0 mg/kg resulted in a dose-dependent reduction in plasma calcium levels. 3. The bioavailability of intracolonically administered human calcitonin at doses of 5.0, 1.0 and 0.1 mg/kg was 0.5%, 0.9% and 0.2%, respectively. 4. Immunohistochemistry showed that human calcitonin transport across the rat colon was rapid and that a significant amount was via a transcellular pathway. 5. We conclude that human calcitonin crosses the gastrointestinal tract of rats in significant amounts and that this demonstrates the feasibility of an oral form for clinical use.

Rat brain particulate fraction was found to contain binding sites for 125I-Salmon Calcitonin-I (125I-SCT). Maximum binding occurred in the physiological pH range of 7.25-7.5. The binding reaction proceeded in a temperature-dependent manner. Binding sites were broadly distributed among the various rat brain regions and considerable regional differences existed in the affinity and density as detected by Scatchard analysis. The highest affinity was recorded in the case of the hypothalamus and the lowest in the case of the cerebellum. The KD (nM) and Bmax (pmole/mg protein) estimated for the binding to four regions were as follows: hypothalamus: 1.4 and 0.19, midbrain, hippocampus plus striatum: 1.5 and 0.08, pons plus medulla oblongata: 3.0 and 0.15 and cerebellum: 8.3 and 0.20. Using a particulate fraction of rat brain void of cerebellum and cortices, a binding assay for calcitonins was developed. Binding of 125I-SCT was inhibited by unlabeled salmon, [Asu1,7]-eel and porcine calcitonins in a dose-dependent manner and the IC50s were 2.0, 8.0 and 30 nM, respectively. The IC50s were comparable to those estimated using a kidney particulate fraction. Human calcitonin, beta-endorphin and substance P were weak inhibitors of the binding. Other peptides, drugs and putative neurotransmitters tested (totally 23 substances) failed to inhibit the binding at concentrations of 1.0 microM. The physiological significance of brain binding sites for calcitonin, with the possibility that the brain may possess endogenous ligands for these sites are discussed.