Direct in vivo demonstration by radioautography of specific binding sites for calcitonin in skeletal and renal tissues of the rat.

Abstract

An in vivo binding assay using radioautography was employed to visualize calcitonin receptors in rat tissues . At 2 min after intravenous injection of biologically active '25 I-salmon calcitonin, free hormone was separated from bound hormone by intracardiac perfusion with lactated Ringer's followed by fixation with 2 .5% glutaraldehyde . Various tissues were removed and processed for light and electron microscope radioautography . These were compared to tissues removed from animals that received identical amounts of labeled hormone with a large excess of unlabeled calcitonin. Among the tissues investigated, kidney and bone demonstrated labeling . In kidney, most silver grains were located over vesicles below the brush border of cells of the proximal convoluted tubules . These grains were still present after simultaneous injection of excess unlabeled hormone and most likely represented binding to sites involved with ingestion and degradation of hormone from the urinary filtrate . In contrast, grains localized to the basal surfaces of distal convoluted tubule cells were significantly reduced in number in control animals and represented sites of saturable, specific hormone binding . In bone, specific binding sites were found only at the periphery of osteoclasts. These labeled cells were located at resorption sites examined in tibia, humerus, and alveolar bone . This demonstration of the localization of ' 25 I-calcitonin in situ provides a new approach for studying the interaction of calciumregulating hormones with their target cells .

Human placental calcitonin receptors

“…Subsequent investigations have shown that the osteoclast [2][3][4][5] and renal tubular cells [6][7][8][9] are major target cells. Nevertheless, a number of other tissues possess CT receptors, including brain [10][11][12], lung [13], testes [14], and trout gill [15] as well as cell lines derived from a wide range of neoplasias including human breast [16], lung [17], and renal carcinoma [18], leukaemia [19,20], teratocarcinoma [21] and osteogenic sarcoma [22].…”

Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

“…Calcitonin is a peptide hormone produced by the thyroid parafollicular cells, commonly named 'C-cells,' that regulate calcium homeostasis (Warshawsky et al 1980). Increases in serum calcium activate the release of calcitonin from the C-cells, which consecutively inhibits bone resorption by the osteoclast and calcium absorption by the intestine.…”

Purification and characterization of calcitonin receptors in rat kidney membranes by covalent cross‐linking techniques

“…The membranes were incubated with the reagent for 2 rnin on ice in a darkened room and then irradiated for 8 rnin with a Hanovia 140-W mercury arc lamp placed 15 cm from the membrane suspension. Tris/HCl (pH 7 h) ('hemic.ol method. Dissuccinimidyl suberate treatment was carried out using the method of Pilch and Czech [25].…”