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C Charles, Christchurch Cardioendocrine Research Group, University of Otago Christchurch, Christchurch, New Zealand
T Katafuchi, Department of Pharmacology, National Cardiovascular Center Research Institute, Suita, 565-8565, Japan
T Yandle, Christchurch Cardioendocrine Research Group, University of Otago Christchurch, Christchurch, New Zealand
N Minamino, Department of Pharmacology, National Cardiovascular Center Research Institute, Suita, Japan

Correspondence: Takeshi Katafuchi, Email: katafuch{at}ri.ncvc.go.jp

Abstract

We have recently reported the isolation of three new members of the calcitonin gene related peptide (CGRP) family of peptides, the calcitonin receptor stimulating peptides (CRSPs). We now report the sequencing and characterisation of ovine/caprine CRSP-1 and caprine CRSP-2. Mature ovine and caprine CRSP-1 are identical and have strong structural homology to CRSP-1s identified to date from other species. As with other CRSP-1s, ovine/caprine CRSP-1 binds to and activates the calcitonin receptor (CT-R) but not the calcitonin-like receptor (CL-R) in combination with the receptor activity-modifying proteins (RAMPs). By contrast, caprine CRSP-2 does not activate any of these receptor-RAMP complexes. Intravenous infusions of ovine CRSP-1 to normal conscious sheep induced dose dependent reductions in plasma total calcium (Ca) levels (p=0.02) and corrected Ca levels (p=0.017) associated with increases in plasma cyclic adenosine monophosphate (cAMP, p=0.002). CRSP-1 reduced both plasma amino-terminal pro-C-type natriuretic peptide levels (p=0.006) and plasma renin activity (p=0.028). There were no significant effects observed on haemodynamic or renal indices measured. In conclusion, we have sequenced ovine/caprine CRSP-1and caprine CRSP-2 precursors. This newly identified CRSP-1 has been shown to share the structural and biological features of CRSP-1s known to date. In vivo studies confirm that ovine CRSP-1 reduces plasma Ca levels in sheep, presumably via a cAMP mediated mechanism. By contrast, caprine CRSP-2 did not stimulate any combination of CT-R, CL-R and RAMPs.