Comparison of the in vitro and in vivo pharmacology of adrenomedullin, calcitonin gene-related peptide and amylin in rats

Abstract

Adrenomedullin has been reported to be structurally similar to a group of peptides that includes amylin, calcitonin and calcitonin gene-related peptide (CGRP). Human and rat adrenomedullin displaced [ 125I]CGRP from membranes of SK-N-MC cells (CGRP receptors) with affinities intermediate between those of rat amylin and rat CGRPα ( K i values 0.12 ± 0.06, 0.017 ± 0.007, 3.83 ± 1.14 and 0.007 ± 0.001 nM, respectively). In contrast, K i values for displacement of [ 125I]rat amylin from nucleus accumbens membranes (amylin receptors), and [ 125I]salmon calcitonin from T47D cells (calcitonin receptors) were lower than with rat amylin or rat CGRPα in these preparations (51 ± 5, 34 ± 2, 0.024 ± 0.002, 0.31 ± 0.07 nM, respectively, at amylin receptors; 33 ± 5, 69 ± 29, 2.7 ± 1.5 and 13 ± 3 nM, respectively, at calcitonin receptors). In anesthetized rats, the hypotensive potency of adrenomedullin was between that of amylin and CGRPα. In contrast, for amylin or calcitonin agonist actions (inhibition of [ 14C]glycogen formation in soleus muscle, hyperlactemia, hypocalcemia and inhibition of gastric emptying), human adrenomedullin was without measurable effect. Thus, in its binding behaviour and in its biological actions, adrenomedullin appeared to behave as a potent CGRP agonist, but as a poor amylin or calcitonin agonist.