Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture

Aliapoulios, Menelaos A.; Goldhaber, Paul; Munson, Paul L.

doi:10.1126/science.151.3708.330

Cited by 210 publications

(43 citation statements)

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“…1) CT receptor is abundantly expressed on osteoclast cells (35). Treatment of resorbing bones with CT increases loss of the ruffled border of the osteoclast cells and decreases the release of lysosomal enzymes from them, which results in a reduction in the plasma calcium level (16,17). 2) Renal tubular epithelia express CT receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Calcitonin (CT) also potently increases the cAMP production in LLC-PK 1 cells (15). CT is secreted mainly from the thyroid gland and is involved in calcium resorption in the bone (16,17) as well as calcium reabsorption in the kidney (18). The CT receptor is also a member of the G-protein-coupled receptor family, and its cDNA clone was first isolated from a cDNA library constructed from LLC-PK 1 cells (19).…”

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confidence: 99%

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Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Katafuchi

Kikumoto

Hamano

et al. 2003

Journal of Biological Chemistry

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We isolated a novel biologically active peptide, designated calcitonin receptor-stimulating peptide (CRSP), from the acid extract of the porcine brain by monitoring cAMP production in the porcine kidney cell line LLC-PK 1 . Determination of the amino acid sequence and cDNA analysis encoding a CRSP precursor showed that this peptide has ϳ60% identity in the amino acid sequence with human calcitonin gene-related peptide type-␣ (␣CGRP), type-␤ (␤CGRP), and porcine CGRP. Northern blot analysis and radioimmunoassay demonstrated that CRSP is expressed mainly in the thyroid gland and the central nervous system, in which the calcitonin receptor was abundantly expressed. Synthetic CRSP elicited a potent stimulatory effect on the cAMP production in LLC-PK 1 cells. Although it shows significant sequence similarity with CGRPs, this peptide did not elicit cAMP elevation in cells that endogenously expressed a CGRP receptor or an adrenomedullin receptor or were transfected with either of these recombinant receptors. Administration of CRSP into anesthetized rats did not alter the blood pressure but induced a transient decrease in the plasma calcium concentration. In fact, this peptide potently increased the intracellular cAMP concentration in COS-7 cells that expressed the recombinant calcitonin receptor. These unique properties indicate that CRSP is not a porcine counterpart of ␤CGRP and probably elicits its biological effects via the calcitonin receptor.Isolation and sequence determination of new biologically active peptides have greatly advanced our understanding of the communication between cells and tissues. Various biologically active peptides, such as natriuretic peptides (1-3) and neuromedins (4), were isolated by monitoring smooth muscle contraction and relaxation. This strategy was useful, but relatively large amounts of tissue extracts were required to monitor the biological activities. Another strategy involving the measurement of intracellular second messenger levels has often been adopted in recent purification studies, and two methods have been successful to date. The first method is to monitor the second messenger levels in intact cultured cells obtained from a particular organ. Pituitary adenylate cyclase-activating peptide and adrenomedullin (AM) 1 were identified by monitoring the adenylyl cyclase activity in the anterior pituitary cells (5) and platelets (6), respectively. The second method is to monitor the second messenger levels in cells expressing a particular orphan receptor. Orexins and ghrelin were purified by monitoring a transient intracellular calcium elevation in HEK293 cells expressing OX 1 R or OX 2 R receptor (7) and growth hormone secretagogue receptor (8), respectively.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Katafuchi

Kikumoto

Hamano

et al. 2003

Journal of Biological Chemistry

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“…Direct evidence for such a mechanism was obtained in tissue culture by Friedman and Raisz (1965), Aliapoulios et al (1966), Gaillard (1966) and Reynolds et al (1968). The administration of phosphate has also been shown to lower blood calcium probably through increasing deposition of bone salt.…”

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confidence: 82%

“…The combination of the two parameters, gross appearance of the calvariae stained by the Von Kossa method and the release of previously incorporated Ca45 in the medium enabled us to show the small difference in the bone resorption much more quantitatively. Considerable evidence for the inhibitory effect of TC on bone resorption has already been presented through studies in vivo (Milhaud, 1968;Johnston,1966;Wallach, 1967;Martin, 1966;O'riordan, 1966) and in vitro (Friedman et al, 1965;Aliapoulios et al , 1966;Gaillard, 1966;Reynolds et al, 1968).…”

Section: Discussionmentioning

confidence: 99%

Pyrophosphate Enhancement of Thyrocalcitonin Effect in Tissue Culture

1969

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SynopsisIn vitro bone culture technique was developed by the modification of the Goldhaber's method. Using this method, pyrophosphate was found to inhibit PTH induced bone resorption as judged by the release of previously incorporated Ca45 into the medium and by the histological findings. Furthermore, addition of pyrophosphate markedly enhanced the thyrocalcitonin inhibition of bone resorption in this system. These findings, together with the previous findings that pyrophosphate enhances the hypocalcemic response to TC in vivo, strongly suggest the favorable effect of the combined use of pyrophosphate and TC in the bone diseases characterized by excessive bone resorption.

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“…Besides lowering serum Ca in various species (Hirsch et al, 1964;Munson and Hirsch, 1966), thyrocalcitonin is known to act on the bone inhibiting resorption (Raisz and Au, 1967;Aliapoulios et al, 1966). However, the action of thyrocalcitonin on other tissues has not yet been studied in detail, except for the possible action on the calcium content of the kidney and cutaneous calcinosis (Selye et al 1967).…”

Section: Discussionmentioning

confidence: 99%

Effect of Age and Thyrocalcitonin on Myocardial Changes Induced by Sodium Sulfaacetylthiazole

et al. 1968

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SYNOPSISNa-sulfaacetylthiazole, 0.5g/kg body weight, was injected into immature and adult rats to produce obstructive nephropathy. Necrotic changes in the myocardium were found in all of the 9 adult rats of about 120days of age, whereas no such changes occured in immature animals of about 40days of age. Thyrocalcitonin, 50 mMRC units a day injected subcutaneously for one week, completely inhibited the occurrence of such myocardial lesion in adult animals, as did parathyroidectomy performed one week previously. Serum calcium was decreased from the normal adult level in thyrocalcitonin treated or parathyroidectomized animals but not in untreated immature rats. Thyrocalcitonin appears to have some effect on cardiovascular system in addition to the known effect on the bone.

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Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture

Abstract: Added thyrocalcitonin greatly diminished parathyroid-hormone-induced resorption of bone in tissue culture. The results indicate that bone is primary site of action of thyrocalcitonin.

Cited by 210 publications

References 3 publications

Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Pyrophosphate Enhancement of Thyrocalcitonin Effect in Tissue Culture

Effect of Age and Thyrocalcitonin on Myocardial Changes Induced by Sodium Sulfaacetylthiazole

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