The CGRP antagonist, CGRP8 - 37, antagonized the ability of CGRP to in
crease blood flow in human skin and cause erythema. The mechanism of t
he antagonist effect of CGRP8 - 37 on the CGRP-induced erythema was an
increase by the antagonist of the rate of decay of the CGRP-induced e
rythema. Since CGRP8 - 37 activates rat peritoneal mast cells to relea
se their granular contents, we conclude that the antagonism by CGRP8 -
37 of the effect of CGRP in human skin is caused by an increase in th
e rate of degradation of CGRP by protease released from skin mast cell
s by CGRP8 - 37. It was not possible to demonstrate any antagonistic e
ffect of CGRP8 - 37 on the CGRP receptor mediating increased blood flo
w in human skin.