Calcitonin receptor-stimulating peptide, a new member of the calcitonin gene-related peptide family: Its isolation from porcine brain, structure, tissue distribution, and biological activity

Takeshi Katafuchi, Katsuro Kikumoto, Kazumasa Hamano, Kenji Kangawa, Hisayuki Matsuo, Naoto Minamino

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12046-12054
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number14
DOIs
StatePublished - Apr 4 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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