RESUMO
Data are presented on the whole-body retention of 133Ba (half-life 10.74 y), over periods of up to 13 y after injection into six healthy male volunteers aged 25-81, and on their levels of biochemical markers for bone turnover. The results are relevant to propositions underlying the ICRP's current (Publication 67) and former (Publication 20) models of alkaline earth metabolism. The tracer was predominantly skeletal within weeks of the injection, as predicted in the current model. The mean retention accorded satisfactorily throughout with predictions based on the current model, but this accord does not necessarily validate the model, for two reasons. First, parameter values attributed to barium were influenced by data emerging during the early years of this study. Second, bone resorption rates in these subjects, as indicated by urinary markers, appear insufficient to explain the long-term reductions in skeletal retention which, in the present model, arise exclusively through this mechanism.
Assuntos
Radioisótopos de Bário/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Fosfatase Alcalina/urina , Aminoácidos/sangue , Aminoácidos/urina , Radioisótopos de Bário/administração & dosagem , Densidade Óssea , Osso e Ossos/metabolismo , Colágeno/sangue , Colágeno/urina , Colágeno Tipo I/sangue , Colágeno Tipo I/urina , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteocalcina/urina , Peptídeos/sangue , Peptídeos/urina , Distribuição TecidualRESUMO
We have examined the in vivo effects in chicks of intravenously injected chicken (c-) and rat (r-) calcitonin gene-related peptides (CGRP) on uptake into bone of a simultaneously administered 45Ca label. Both peptides caused transient (10 min) increases in 45Ca uptake into a variety of bone types. In dose-response experiments at 10 min, CGRP doses of 0.26-1.04 nmol/100 g body wt were found to give maximal responses. These were well developed in chicks fasted for 22 h but absent in those which were continuously fed. This contrasts with the hypercalcaemic effect of CGRP which is apparent in fed rather than fasted chicks.
Assuntos
Osso e Ossos/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Cálcio/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Osso e Ossos/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/administração & dosagem , Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Galinhas , Relação Dose-Resposta a Droga , Jejum , FemininoRESUMO
In vivo effects of intravenously injected chicken(c-) and rat(r-) calcitonin gene related peptide (CGRP) upon plasma total (Cat), ionized (Cai) calcium, inorganic phosphate (Pi) and clearance of an acutely administered 45Ca label have been examined in chicks. Both peptides were hypercalcaemic in fasted chicks, unlike previously reported hypocalcaemic response in mammals. r-CGRP was hypercalcaemic at doses of both 0.26 and 1.31 nmol/100 g body wt, the lower dose produced a significant elevation of Cat one hour after injection into 12-h-fasted chicks, the upper dose had a similar effect at 20 min. Cai was also non-significantly elevated by r-CGRP. Pi was slightly increased by r-CGRP at both doses, 20 and 60 min after injection. c-CGRP produced a dose (0.26-4.17 nmol/100 g body wt) dependent elevation of Cat and Cai in 22-h-fasted chicks. A greater response was however seen in fed animals. Peak responses were observed 45 min after injection. c-CGRP (1.04 nmol/100 g body wt) caused a significant decline in plasma Pi (P less than 0.05) in fasted chicks. Pi was elevated in control fed animals compared with fasted controls. c-CGRP (1.04 nmol/100 g) did not effect plasma Pi in fed chicks. Whilst both peptides elevated plasma Ca, clearance of an acutely administered 45Ca label from plasma was greater in both r-CGRP treated 12-h-fasted chicks and c-CGRP treated 22-h-fasted chicks. In contrast, the rate of 45Ca clearance in fed chicks was not affected by c-CGRP treatment. The differential effects of these peptides upon plasma 45Ca clearance and other plasma parameters of Ca metabolism, suggest a complex mode of action of the peptide upon avian Ca homeostasis, possibly involving direct actions upon kidney and bone.