TY - JOUR
T1 - Calcitonin receptor-stimulating peptide, a new member of the calcitonin gene-related peptide family
T2 - Its isolation from porcine brain, structure, tissue distribution, and biological activity
AU - Katafuchi, Takeshi
AU - Kikumoto, Katsuro
AU - Hamano, Kazumasa
AU - Kangawa, Kenji
AU - Matsuo, Hisayuki
AU - Minamino, Naoto
PY - 2003/4/4
Y1 - 2003/4/4
N2 - We isolated a novel biologically active peptide, designated calcitonin receptor-stimulating peptide (CRSP), from the acid extract of the porcine brain by monitoring cAMP production in the porcine kidney cell line LLC-PK1. Determination of the amino acid sequence and cDNA analysis encoding a CRSP precursor showed that this peptide has ∼60% identity in the amino acid sequence with human calcitonin gene-related peptide type-α (αCGRP), type-β (βCGRP), and porcine CGRP. Northern blot analysis and radioimmunoassay demonstrated that CRSP is expressed mainly in the thyroid gland and the central nervous system, in which the calcitonin receptor was abundantly expressed. Synthetic CRSP elicited a potent stimulatory effect on the cAMP production in LLC-PK1 cells. Although it shows significant sequence similarity with CGRPs, this peptide did not elicit cAMP elevation in cells that endogenously expressed a CGRP receptor or an adrenomedullin receptor or were transfected with either of these recombinant receptors. Administration of CRSP into anesthetized rats did not alter the blood pressure but induced a transient decrease in the plasma calcium concentration. In fact, this peptide potently increased the intracellular cAMP concentration in COS-7 cells that expressed the recombinant calcitonin receptor. These unique properties indicate that CRSP is not a porcine counterpart of βCGRP and probably elicits its biological effects via the calcitonin receptor.
AB - We isolated a novel biologically active peptide, designated calcitonin receptor-stimulating peptide (CRSP), from the acid extract of the porcine brain by monitoring cAMP production in the porcine kidney cell line LLC-PK1. Determination of the amino acid sequence and cDNA analysis encoding a CRSP precursor showed that this peptide has ∼60% identity in the amino acid sequence with human calcitonin gene-related peptide type-α (αCGRP), type-β (βCGRP), and porcine CGRP. Northern blot analysis and radioimmunoassay demonstrated that CRSP is expressed mainly in the thyroid gland and the central nervous system, in which the calcitonin receptor was abundantly expressed. Synthetic CRSP elicited a potent stimulatory effect on the cAMP production in LLC-PK1 cells. Although it shows significant sequence similarity with CGRPs, this peptide did not elicit cAMP elevation in cells that endogenously expressed a CGRP receptor or an adrenomedullin receptor or were transfected with either of these recombinant receptors. Administration of CRSP into anesthetized rats did not alter the blood pressure but induced a transient decrease in the plasma calcium concentration. In fact, this peptide potently increased the intracellular cAMP concentration in COS-7 cells that expressed the recombinant calcitonin receptor. These unique properties indicate that CRSP is not a porcine counterpart of βCGRP and probably elicits its biological effects via the calcitonin receptor.
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U2 - 10.1074/jbc.M207970200
DO - 10.1074/jbc.M207970200
M3 - Article
C2 - 12556539
AN - SCOPUS:0038187671
SN - 0021-9258
VL - 278
SP - 12046
EP - 12054
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -