Pharmacologic study of C-terminal fragments of frog skin calcitonin gene-related peptide.
The calcitonin gene-related peptide from the skin of the frog Phyllomedusa bicolor (pbCGRP) is a 37-residue neuropeptide that differs from human alpha CGRP (halphaCGRP) at 16 positions. The affinities of the C-terminal fragments of pbCGRP and halphaCGRP were evaluated in SK-N-MC cells: pbCGRP(8-37) (K(i)=0.2nM) and pbCGRP(27-37) (K(i)=95nM) were, respectively, 3 times and 20 times more potent than the human fragments halphaCGRP(8-37) and halphaCGRP(27-37). Their antagonistic potencies were measured in SK-N-MC and Col 29 cells, and the rat vas deferens. pbCGRP(8-37) inhibited the halphaCGRP-stimulated production of cAMP by SK-N-MC and Col 29 cells 3 to 4 times more strongly than halphaCGRP(8-37). Thus pbCGRP(8-37) is the most potent CGRP-1 competitive antagonist of all the natural sequences reported to date. pbCGRP(27-37) was also as potent as [D(31), A(34), F(35)] halphaCGRP(27-37), a prototypic antagonist analog derived from structure-activity relationship studies of halphaCGRP(8-37).
Ladram
Ali
A
Peptidome de la Peau des Amphibiens, FRE2852, Université Pierre et Marie Curie - Paris 6, Tour 43, 2 Place Jussieu, 75251 Paris Cédex 05, France. ladram@ccr.jussieu.fr
Besné
Isabelle
I
Breton
Lionel
L
de Lacharrière
Olivier
O
Nicolas
Pierre
P
Amiche
Mohamed
M
D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry* / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002460:Cell Line; D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012867:Skin / Q000737:chemistry*; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide