Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens

Poyner, David R., Taylor, Gillian M., Tomlinson, A. Elaine, Richardson, Alan G. and Smith, David M. (1999). Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens. British Journal of Pharmacology, 126 (5), pp. 1276-1282.

Abstract

1. The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD 2s for CGRP, amylin and adrenomedullin of 7.90 ± 0.11, 7.70 ± 0.19 and 7.25 ± 0.10 respectively). 3. CGRP 8-37 (1 μM) and AC187 (10 μM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin 22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [ 125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC 50 of 8.91 and a capacity of 643 fmol mg -1. Its selectivity profile was adrenomedullin > AC187 > CGRP = amylin. It was clearly distinct from a site labelled by [ 125I]-CGRP (pIC 50 = 8.73, capacity = 114 fmol mg -1, selectivity CGRP > amylin = AC187 > adrenomedullin). [ 125I]-amylin bound to two sites with a total capacity of 882 fmol mg -1. 6. Although CGRP has been shown to act at a CGRP 2 receptor on the vas deferens with low sensitivity to CGRP 8-37, this antagonist displaced [ 125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4°C to 25°C, suggesting the anomalous behaviour of CGRP 8-37 is not due to temperature differences between binding and functional assays.

Publication DOI: https://doi.org/10.1038/sj.bjp.0702437
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Uncontrolled Keywords: adrenomedullin,amylin,CGRP,CGRP receptor,guinea-pig,vas deferens,Pharmacology
Full Text Link: http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0702437/abstract
Related URLs: http://www.scopus.com/inward/record.url?scp=0033043673&partnerID=8YFLogxK (Scopus URL)
Published Date: 1999-03-22
Authors: Poyner, David R. ( 0000-0003-1590-112X)
Taylor, Gillian M.
Tomlinson, A. Elaine
Richardson, Alan G.
Smith, David M.

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