Calcitonins and Calcitonin Precursors Peptides

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Introduction

Calcitonin is a polypeptide hormone consisting of 32 amino acids that inhibits bone resorption by inhibiting the activity of osteoclasts. In humans, the precursor of calcitonin is a glycoprotein. The carboxy terminal is a precursor of glycine by protease cleavage. Further, it is processed into a mature calcitonin having an amide group at the carboxy terminal by the action of peptidylglycine α-amidase. Calcitonin was first discovered by Hirsh and demonstrated its calcium-phosphorus metabolism regulation. It has shown good results in the treatment of osteoporosis, hypercalcemia, hyperparathyroidism, osteoarthritis and bone healing. The clinically used calcitonin is mainly a non-human calcitonin isolated and purified from the squid and porcine thyroid gland.

Mechanism of action

Studies have shown that calcitonin-induced signaling regulates the excitability of primary afferents via the calcitonin receptor, thereby controlling Na⁺ channel transcription in the dorsal root ganglia. The accumulation and maintenance of calcitonin-induced signals and the further breakdown of the calcitonin receptor-mediated system in peripheral nerve tissue are one of the strategies for relieving neuropathic pain. Ito et al reported that in ovariectomized-induced hyperalgesia rats, treatment with calcitonin at the end of the spinal cord in response to pain increased the level of high-threshold Na⁺ channel expression. This indicates that the recovery of the descending inhibition system is also conducive to the appearance of the analgesic effect.

Application of Calcitonins and Calcitonin Precursors Peptides

Studies have shown that calcitonin selectively improves the chronic contractile injury of rats to enhance the arterial contractility, thereby exerting its mitigation effect on peripheral circulatory disorders. Calcitonin increases the level of endogenous opioid metabolites and thus acts to relieve pain. Osteoporosis causes vertebral deformation and ultimately leads to small joint damage. Lumbar osteoporosis causes microfracture of the vertebral body, resulting in loss of vertebral height, disorder of intervertebral disc and facet joint, and triggering arthritis. Calcitonin is used to treat osteoporosis by promoting bone mineralization and improving bone structure. Calcitonin and its precursor peptides have a good effect on the symptoms of bone pain caused by many bone metabolic diseases.

Reference

1. Hirsch, P.F., Munson, P.L. (1969) Thyrocalcitonin. Physiol Rev, 49(3): 548-622.