期刊论文详细信息
FEBS Letters
Molecular and functional characterization of a partial cDNA encoding a novel chicken brain melatonin receptor
Lee, F.J.S.3  Niznik, H.B.2  Pang, S.F.4  Pristupa, Z.B.2  Hamadanizadeh, A.3  Yuan, H.1  Brown, G.M.2  Sugamori, K.S.3  Liu, F.5 
[1] Laboratory of Neuro-Endocrinology, Clarke Institute of Psychiatry, Toronto, Ontario M5T 1R8, Canada;Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada;Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada;Department of Physiology, University of Hong Kong, Hong Kong;Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
关键词: G-protein coupled;    cAMP inhibition;    Dopamine D1 receptor;   
DOI  :  10.1016/0014-5793(95)01129-3
学科分类:生物化学/生物物理
来源: John Wiley & Sons Ltd.
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【 摘 要 】

An approach based on homology probing was used to clone a partial cDNA encoding a novel melatonin (ML) receptor (MLR) from chicken (Gallus domesticus) brain. Based on available deduced amino-acid sequence, the chicken MLR (cMLR) displayed greater sequence homology to the frog (Xenopus) MLR than cloned human/mammalian receptors, with overall identities of 73% and 66%, respectively. In order to gain functional expression, a chimeric frog/chicken (flc)MLR was constructed in which the 5′ end of the cMLR, including the N-terminus, TM1 and part of the first intracellular loop was substituted by fMLR sequence. [125I]Iodo-ML bound with high affinity (K d of ∼35 pM) to COS-7 cells transiently expressing the flcMLR in a saturable and guanine nucleotide-sensitive manner with the following rank order of potency: 2-iodo-ML > ML > 6-Cl-ML > S20750 > 6-OH-ML > S20643 > S20753 > N-acetyl-5HT > > 5-HT. Estimated K i values for these compounds at the flcMLR correlated well to those obtained in native chicken brain membranes. In line with the observed structural similarity to the fMLR, the flcMLR exhibited affinities for ML, 6-Cl-ML and 6-OH-ML ∼10-fold lower than mammalian receptors. Functionally, opposing interactions between ML and dopamine receptor signal transduction pathways were observed with ML potently inhibiting dopamine D1A-receptor-mediated cAMP accumulation in cells (HEK-293) transiently co-expressing these receptors. cMLR mRNAs were found expressed in chicken brain and kidney with trace levels observed in the lung. The availability of cloned vertebrate MLRs distinct at both the amino acid and pharmacological level from their mammalian counterparts may now allow for the identification of those amino-acid residues and structural motifs that regulate ML-binding specificity and affinity.

【 授权许可】

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