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.
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-PK(1). Determination of the amino acid sequence and cDNA analysis encoding a CRSP precursor showed that this peptide has approximately 60% identity in the amino acid sequence with human calcitonin gene-related peptide type-alpha (alphaCGRP), type-beta (betaCGRP), 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-PK(1) 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 betaCGRP and probably elicits its biological effects via the calcitonin receptor.
Katafuchi
Takeshi
T
National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita 565-8565, Osaka, Japan.
Kikumoto
Katsuro
K
Hamano
Kazumasa
K
Kangawa
Kenji
K
Matsuo
Hisayuki
H
Minamino
Naoto
N
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry; D019556:COS Cells; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D018374:LLC-PK1 Cells; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D014162:Transfection
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D011994:Recombinant Proteins; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium