Article date: March 1999
By: David R Poyner, Gillian M Taylor, A Elaine Tomlinson, Alan G Richardson, David M Smith, in Volume 126, Issue 5, pages 1276-1282
The receptors which mediate the effects of calcitonin gene‐related peptide (CGRP), amylin and adrenomedullin on the guinea‐pig vas deferens have been investigated.
All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90±0.11, 7.70±0.19 and 7.25±0.10 respectively).
CGRP8–37 (1 μM) and AC187 (10 μM) showed little antagonist activity against adrenomedullin.
Adrenomedullin22–52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin.
[125I]‐adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 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 (pIC50=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.
Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8–37, 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 CGRP8–37 is not due to temperature differences between binding and functional assays.
The receptors which mediate the effects of calcitonin gene‐related peptide (CGRP), amylin and adrenomedullin on the guinea‐pig vas deferens have been investigated.
All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90±0.11, 7.70±0.19 and 7.25±0.10 respectively).
CGRP8–37 (1 μM) and AC187 (10 μM) showed little antagonist activity against adrenomedullin.
Adrenomedullin22–52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin.
[125I]‐adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 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 (pIC50=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.
Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8–37, 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 CGRP8–37 is not due to temperature differences between binding and functional assays.
British Journal of Pharmacology (1999) 126, 1276–1282; doi:10.1038/sj.bjp.0702437
DOI: 10.1038/sj.bjp.0702437
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