The CALC-I gene gives rise to more than one bioactive peptide: CT and CGRP. This occurs because of alternative processing of the primary RNA transcript72 (see Chap. 3; see Fig. 53-1).

Two very similar human CGRPs are found: CGRP-I (or α) from the CALC-I gene and CGRP-II (or β) from the CALC-II gene. CGRP-I is a 37-amino-acid hormone; in humans, CGRP-II differs from CGRP-I by only three amino acids (see Fig. 53-2).73 The CGRPs have only a modest homology with CT. As is the case for CT, however, the CGRPs have an NH ₂-terminal disulfide bridge and a COOH-terminal amide. The CALC-II gene does not seem to be alternatively expressed. The CALC-I and CALC-II genes, plus a pseudogene, CALC-III, probably arose by local duplication of a common ancestral gene.74 Unlike with CT, the structure of the CGRPs is highly conserved in different animal species.

CT and CGRP-I can be coexpressed by a single cell, and several tissues contain both of them.75 However, usually a preference is seen for synthesis of either CT or CGRP-I according to the cellular type and localization. In the C cell, CT is preferentially produced; in the nervous system, CGRP-I predominates. The decision concerning the prevailing mode of synthesis is not immutable; for example, it can be modified by dexamethasone and by the naturally occurring fatty acid butyrate. Whether the expression of CALC-I and CALC-II genes is independently regulated is uncertain.