Biology of peptides from the calcitonin genes.

Despite being products from the same gene, there is clearly a marked divergence in the distribution and physiological role of calcitonin and CGRP. Whereas calcitonin is predominantly distributed in the thyroid, CGRP is abundant in the nervous system throughout the body. Though the peptides have only weak structural homologies, a generally similar conformation enables them to interact at each other's receptors. Hence the pharmacological effects of the peptides faintly resemble one another. Calcitonin receptors are mainly found on osteoclasts and at certain sites in the nervous system. CGRP binding sites are abundant in the cerebellum and blood vessels. Calcitonin is a circulating hormone controlling osteoclastic activity. CGRP acts as a neurotransmitter or neuromodulator centrally, and released from perivascular nerve terminals, it modulates arteriolar tone. Released from motoneurones, CGRP may also play a trophic role regulating the muscle acetylcholine receptor state. The next decade should establish the physiological role of CGRP and the regulation of the expression of the calcitonin/CGRP gene complex.