Structural determinants for binding to CGRP receptors expressed by human SK-N-MC and Col 29 cells:Studies with chimeric and other peptides

Poyner, David R., Soomets, Ursel, Howitt, Stephen G. and Langel, Ulo (1998). Structural determinants for binding to CGRP receptors expressed by human SK-N-MC and Col 29 cells:Studies with chimeric and other peptides. British Journal of Pharmacology, 124 (8), pp. 1659-1666.

Abstract

1. Structure-activity relationships for the binding of human α-calcitonin gene-related peptide 8-37 (hαCGRP8-37) have been investigated at the CGRP receptors expressed by human SK-N-MC (neuroblastoma) and Col 29 (colonic epithelia) cells by radioligand binding assays and functional assays (hαCGRP stimulation of adenylate cyclase). 2. On SK-N-MC cells the potency order was hαCGRP8-37 > hαCGRP19-37 = AC187 > rat amylin8-37 > hα[Tyr0]-CGRP28-37 (apparent pKBS of 7.49 ± 0.25, 5.89 ± 0.20, 6.18 ± 0.19, 5.85 ± 0.19 and 5.25 ± 0.07). The SK-N-MC receptor appeared CGRP1-like. 3. On Col 29 cells, only hαCGRP8-37 of the above compounds was able to antagonize the actions of hαCGRP (apparent pKB = 6.48 ± 0.28). Its receptor appeared CGRP2-like. 4. hα[Ala11,18]-CGRP8-37, where the amphipathic nature of the N-terminal α-helix has been reduced, bound to SK-N-MC cells a 100 fold less strongly than hαCGRP8-37. 5. On SK-N-MC cells, hαCGRP(8-18, 28-37) (M433) and mastoparan-hαCGRP28-37 (M432) had apparent pKBS of 6.64 ± 0.16 and 6.42 ± 0.26, suggesting that residues 19-27 play a minor role in binding. The physico-chemical properties of residues 8-18 may be more important than any specific side-chain interactions. 6. M433 was almost as potent as hαCGRP8-37 on Col 29 cells (apparent pKB = 6.17 ± 0.20). Other antagonists were inactive.

Publication DOI: https://doi.org/10.1038/sj.bjp.0702032
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Uncontrolled Keywords: calcitonin gene-related peptide,CGRP antagonist,CGRP receptor,chimeric peptide,mastoparan,Pharmacology
Full Text Link: http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0702032/abstract
Related URLs: http://www.scopus.com/inward/record.url?scp=0031818614&partnerID=8YFLogxK (Scopus URL)
Published Date: 1998-08-26
Authors: Poyner, David R. ( 0000-0003-1590-112X)
Soomets, Ursel
Howitt, Stephen G.
Langel, Ulo

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