Hc. Champion et al., ADRENOMEDULLIN-(22-52) ANTAGONIZES VASODILATOR RESPONSES TO CGRP BUT NOT ADRENOMEDULLIN IN THE CAT, American journal of physiology. Regulatory, integrative and comparative physiology, 41(1), 1997, pp. 234-242
The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor a
ntagonist, on vasodilator responses to ADM and the structurally relate
d peptide, calcitonin gene-related peptide (CGRP), were investigated i
n the hindlimb vascular bed of the cat under constant-flow conditions.
ADM-(22-52) had no significant effect on hindlimb perfusion pressure
when injected in doses up to 120 nmol; after administration of ADM-(22
-52), vasodilator responses to ADM were unchanged, whereas vasodilator
responses to CGRP were inhibited. The inhibitory effects of ADM-(22-5
2) on responses to CGRP were selective and reversible and were similar
to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlim
b vasodilator responses to CGRP and to ADM were increased in duration
by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase i
nhibitor rolipram but were not altered by inhibitors of guanosine 3',5
'-cyclic monophosphate phosphodiesterase, nitric oxide synthetase, K+-
ATP channels, the cyclooxygenase pathway, or the adrenergic nervous sy
stem. These results demonstrate that ADM-(22-52) is a selective CGRP r
eceptor antagonist in the hindlimb vascular bed of the cat. The presen
t data suggest that vasodilator responses to CGRP and ADM are mediated
by different receptors but that these peptides dilate the hindlimb va
scular bed of the cat by a similar cAMP-dependent mechanism.