A comparison of the actions of BIBN4096BS and CGRP 8-37 on CGRP and adrenomedullin receptors expressed on SK-N-MC, L6, Col 29 and Rat 2 cells

Hay, Debbie L., Howitt, Stephen G., Conner, Alex C., Doods, Henri, Schindler, Marcus and Poyner, David R. (2002). A comparison of the actions of BIBN4096BS and CGRP 8-37 on CGRP and adrenomedullin receptors expressed on SK-N-MC, L6, Col 29 and Rat 2 cells. British Journal of Pharmacology, 137 (1), pp. 80-86.

Abstract

1. The ability of the CGRP antagonist BIBN4096BS to antagonize CGRP and adrenomedullin has been investigated on cell lines endogenously expressing receptors of known composition. 2. On human SK-N-MC cells (expressing human calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1)), BIBN4096BS had a pA 2 of 9.95 although the slope of the Schild plot (1.37±0.16) was significantly greater than 1. 3. On rat L6 cells (expressing rat CRLR and RAMP1), BIBN4096BS had a pA 2 of 9.25 and a Schild slope of 0.89±0.05, significantly less than 1. 4. On human Colony (Col) 29 cells, CGRP 8-37 had a significantly lower pA 2 than on SK-N-MC cells (7.34±0.19 (n=7) compared to 8.35±0.18, (n=6)). BIBN4096BS had a pA 2 of 9.98 and a Schild plot slope of 0.86±0.19 that was not significantly different from 1. At concentrations in excess of 3 nM, it was less potent on Col 29 cells than on SK-N-MC cells. 5. On Rat 2 cells, expressing rat CRLR and RAMP2, BIBN4096BS was unable to antagonize adrenomedullin at concentrations up to 10 μM. CGRP 8-37 had a pA 2 of 6.72 against adrenomedullin. 6. BIBN4096BS shows selectivity for the human CRLR/RAMP1 combination compared to the rat counterpart. It can discriminate between the CRLR/RAMP1 receptor expressed on SK-N-MC cells and the CGRP-responsive receptor expressed by the Col 29 cells used in this study. Its slow kinetics may explain its apparent 'non-competive' behaviour. At concentrations of up to 10 μM, it has no antagonist actions at the adrenomedullin, CRLR/RAMP2 receptor, unlike CGRP 8-37.

Publication DOI: https://doi.org/10.1038/sj.bjp.0704844
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Uncontrolled Keywords: adrenomedullin,BIBN4096BS,CGRP,Col 29,CRLR,L6,RAMP1,RAMP2,SK-N-MC,Pharmacology
Full Text Link: http://www3.interscience.wiley.com/journal/121674353/abstract
Related URLs: http://www.scopus.com/inward/record.url?scp=0036729745&partnerID=8YFLogxK (Scopus URL)
Published Date: 2002-09-16
Authors: Hay, Debbie L.
Howitt, Stephen G.
Conner, Alex C.
Doods, Henri
Schindler, Marcus
Poyner, David R. ( 0000-0003-1590-112X)

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