W. Vine et al., COMPARISON OF THE IN-VITRO AND IN-VIVO PHARMACOLOGY OF ADRENOMEDULLIN, CALCITONIN-GENE-RELATED PEPTIDE AND AMYLIN IN RATS, European journal of pharmacology, 314(1-2), 1996, pp. 115-121
Adrenomedullin has been reported to be structurally similar to a group
of peptides that includes amylin, calcitonin and calcitonin gene-rela
ted peptide (CGRP). Human and rat adrenomedullin displaced [I-125]CGRP
from membranes of SK-N-MC cells (CGRP receptors) with affinities inte
rmediate between those of rat amylin and rat CGRP alpha (K-i values 0.
12 +/- 0.06, 0.017 +/- 0.007, 3.83 +/- 1.14 and 0.007 +/- 0.001 nM, re
spectively). In contrast, K-i values for displacement of [I-125]rat am
ylin from. nucleus accumbens membranes (amylin receptors), and [I-125]
salmon calcitonin from T47D cells (calcitonin receptors) were lower th
an with rat amylin or rat CGRP alpha in these preparations (51 +/- 5,
34 +/- 2, 0.024 +/- 0.002, 0.31 +/- 0.07 nM, respectively, at amylin r
eceptors; 33 +/- 5, 69 +/- 29, 2.7 +/- 1.5 and 13 +/- 3 nM, respective
ly, at calcitonin receptors). In anesthetized rats, the hypotensive po
tency of adrenomedullin was between that of amylin and CGRP alpha. In
contrast, for amylin or calcitonin agonist actions (inhibition of [C-1
4]glycogen formation in soleus muscle, hyperlactemia, hypocalcemia and
inhibition of gastric emptying), human adrenomedullin was without mea
surable effect. Thus, in its binding behaviour and in its biological a
ctions, adrenomedullin appeared to behave as a potent CGRP agonist, bu
t as a poor amylin or calcitonin agonist.