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Structural requirements for the interaction of sheep insulin-like factor 3 with relaxin receptors in rat atria

Citation

Tan, YY and Dawson, NF and Kompa, AR and Bond, CP and Claasz, A and Wade, JD and Tregear, GW and Summers, RJ, Structural requirements for the interaction of sheep insulin-like factor 3 with relaxin receptors in rat atria, European Journal of Pharmacology, 457, (2-3) pp. 153-160. ISSN 0014-2999 (2002) [Refereed Article]


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DOI: doi:10.1016/S0014-2999(02)02662-6

Abstract

Relaxin is a peptide with various reproductive and nonreproductive functions. The site for the peptide–receptor interaction contains two arginines (Arg) and an isoleucine (Ile) or valine (Val) residue in the B-chain with a configuration of -Arg-X-X-X-Arg-X-X-Ile/Val-X-. The sheep insulin-like peptide 3 (INSL3), a structural homologue of relaxin, also contains the n, n + 4 arginines in the B-chain but they are displaced towards the carboxyl terminus by four residues (-X-X-X-X-Arg-X-X-Val-Arg-). Human INSL3 increases the activity of human relaxin in mouse bioassays. Here, we investigated whether sheep synthetic INSL3 affects the relaxin activity in rat atria. INSL3 lacked relaxin-like agonist activity but blocked the activity of relaxin and competed for relaxin binding sites at high concentrations. We also synthesized analogues of INSL3, with amino acid substitutions in the arginine-binding region. Analogues A, D and E, which have the arginines in positions identical to relaxin, showed weak relaxin-like agonist activity. These results suggest that other sites in the relaxin molecule are involved in high-affinity peptide–receptor interaction for the production of the relaxin biological responses.

Item Details

Item Type:Refereed Article
Keywords:relaxin; INSL3 (insulin-like peptide 3), atria, rat, chronotropic, inotropic, receptor autoradiography
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmacology and Pharmaceutical Sciences not elsewhere classified
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Preventive Medicine
Author:Tan, YY (Dr Yean Tan)
ID Code:47836
Year Published:2002
Web of Science® Times Cited:9
Deposited By:Pharmacy
Deposited On:2007-08-01
Last Modified:2012-10-29
Downloads:0

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