Selective antagonism of calcitonin-induced osteoclastic quiescence (Q effect) by human calcitonin gene-related peptide-(Val8Phe37).
Exposure of isolated rat osteoclasts to calcitonin (CT) leads to an abrupt cessation of cell motility (Q effect) followed by cell retraction (R effect). We have previously shown that these effects are mediated by two G proteins that appear to activate separate post-receptor pathways. The present study demonstrates that the Q but not the R effect of CT (0.006 microM) is abolished in the presence of human calcitonin gene-related peptide (CGRP)-(Val8Phe37) (0.5 microM), a fragment analogue of human CGRP. This selective antagonism suggests that the Q effect could result from an action of CT upon a site that is distinct from that producing the R effect. The former site ('amylin site') also appears to interact with related peptides, amylin and CGRP, whilst the latter site ('CT site') specifically interacts with CT.
Alam
A S
AS
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London U.K.
Moonga
B S
BS
Bevis
P J
PJ
Huang
C L
CL
Zaidi
M
M
D000818:Animals; D000831:Animals, Newborn; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D015290:Second Messenger Systems; D013997:Time Factors
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide