hCGRP8-37, a calcitonin gene-related peptide antagonist revealing calcitonin gene-related peptide receptor heterogeneity in brain and periphery.
The C-terminal fragment of human calcitonin gene-related peptide (CGRP), hCGRP8-37, fails to induce any biological activity in a variety of isolated tissues and behavioral assays even though it possesses nanomolar affinity for [125I]hCGRP alpha binding sites in the central nervous system and peripheral membrane preparations. However, hCGRP8-37 displays relatively potent, competitive antagonist properties toward the action of native hCGRP alpha in guinea pig atrial and ileal preparations and on the central nervous system-mediated inhibition of CGRP on food intake. On the contrary, in the rat vas deferens the antagonistic potency of hCGRP8-37 was much weaker and was ineffective against CGRP-induced hyperthermia after i.c.v. injection. Such evidence suggests the existence of at least two classes of CGRP receptors, the first (CGRP1) being sensitive to the antagonist properties of hCGRP8-37, whereas the second (CGRP2) is not. The use of hCGRP8-37 should greatly facilitate the characterization of the physiological roles of CGRP-like peptides, especially those which are mediated via the activation of CGRP1 receptors.
Dennis
T
T
Douglas Hospital Research Centre, McGill University, Verdun, Quebec, Canada.
Fournier
A
A
Cadieux
A
A
Pomerleau
F
F
Jolicoeur
F B
FB
St Pierre
S
S
Quirion
R
R
D000818:Animals; D001923:Brain Chemistry; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects*
D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide