Katacalcin TFA

In contrast to extensive determinations of calcitonin gene-related peptide (CGRP) in neural tissues, calcitonin and its carboxyl-terminal flanking peptide katacalcin (in human PDN-21) have not been systematically measured by radioimmunoassay (RIA) in discrete brain structures. Using microwave irradiation (MW), a procedure that increases the recovery of neuropeptides, we investigated by radioimmunoassay (RIA) the rat brain regional distribution of CGRP like- immunoreactivity (-LI), calcitonin-LI, and katacalcin-LI. Calcitonin-LI and katacalcin-LI were found in low concentrations in frontal cortex, occipital cortex, striatum and hippocampus. Moreover, a 4-week treatment with antipsychotic drugs altered the concentrations of the calcitonin-gene family peptides in the frontal cortex, occipital cortex, and hippocampus; the magnitude of these changes, however, was only moderate. Lastly, calcitonin-LI and katacalcin-LI baseline concentrations as well as after antipsychotic treatment were highly correlated in the frontal cortex, striatum, and hippocampus. The possible regulatory role of calcitonin gene family peptides in the central nervous system (CNS) needs to be further explored.

Calcitonin is used in therapy for osteoporosis and Paget's disease. In vitro, human calcitonin forms thick gels which limits its usefulness as a therapeutic, and consequently salmon calcitonin which is less prone to aggregate is commonly used instead. In order to probe the role of the C-terminal region of the molecule in association and gel formation we have prepared a set of three peptides corresponding to the C-terminal regions of salmon calcitonin, human calcitonin and a mutant of human calcitonin in which Pro-23 is substituted with Ala. The peptides are largely disordered in their monomeric state as judged by CD and FTIR. All three peptides aggregate and form gels. Both human peptides form a gel much faster than the salmon peptide and the proline to alanine mutant forms a gel faster than the wildtype human peptide. Gel formation by all three peptides is slower than for intact human calcitonin. CD indicates a difference in conformation for the human fragment but not for the salmon fragment between the monomeric state and the gel state. FTIR experiments suggest the presence of beta-structure in the gel derived from the human peptide but not in the gel derived from the salmon peptide. These results show that there are clear differences in the association properties of the peptides and point to a potential role for the C-terminal region of calcitonin in controlling aggregation/gel formation.