Calcitonin gene-related peptide is metabolized by an endopeptidase hydrolyzing substance P.
Calcitonin gene-related peptide (CGRP) is cleaved by an endopeptidase, also known to hydrolyze substance P (SP). The enzyme which was isolated from human cerebrospinal fluid, converted rCGRP into two products, clearly separable on HPLC. Amino acid analysis showed cleavage to occur at Leu16-Ser17. The carboxy-terminal fragment, rCGRP-(17-37), was weakly active in inhibiting 125I-rCGRP binding to a rat medulla oblongata membrane preparation, but it showed no binding to spinal cord membranes. The N-terminal fragment, rCGRP-(1-16), had very low or no affinity. Autoradiography with 125I-rCGRP showed distinct labelling of rat dorsal spinal cord, while there was no consistent pattern with 125I-rCGRP-(1-16). In the isolated guinea pig ileum preparation, the two fragments showed no CGRP-like activity. The ability of CGRP to interfere with SP degradation is offered as the explanation why CGRP has been reported to potentiate several biologic actions of SP.
Le Grevès
P
P
Department of Pharmacology, Uppsala, Sweden.
Nyberg
F
F
Hökfelt
T
T
Terenius
L
L
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*
D000596:Amino Acids; D009479:Neuropeptides; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D013373:Substance P; D002116:Calcitonin; D010450:Endopeptidases; D015740:Calcitonin Gene-Related Peptide