COMPARISON OF THE IN-VITRO AND IN-VIVO PHARMACOLOGY OF ADRENOMEDULLIN, CALCITONIN-GENE-RELATED PEPTIDE AND AMYLIN IN RATS

Citation
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
Citations number
33
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
314
Issue
1-2
Year of publication
1996
Pages
115 - 121
Database
ISI
SICI code
0014-2999(1996)314:1-2<115:COTIAI>2.0.ZU;2-X
Abstract
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.