Analysis of the pharmacological properties of chicken melanocortin-2 receptor (cMC2R) and chicken melanocortin-2 accessory protein 1 (cMRAP1)

作者：Barlock Travis K; Gehr Deshae T; Dores Robert M^*

来源：General and Comparative Endocrinology, 2014, 205: 260-267.

DOI：10.1016/j.ygcen.2014.03.045

• Gallus gallus
• Melanocortin-2 receptor
• Melanocortin-2 receptor accessory protein

The chicken (Gallus gallus) melanocortin-2 receptor (cMC2R) can be functionally expressed in CHO cells when chicken melanocortin-2 receptor accessory protein I (cMRAP1) is co-expressed. The transiently transfected CHO cells responded in a robust manner to stimulation by hACTH(1-24) (EC50 value = 2.7 x 10(-12) M +/- 1.3 x 10(-12)), but the transfected CHO cells could not be stimulated by NDP-MSH at concentrations as high as 10(-7) M. Incubation of cMC2R/cMRAP1 transfected cells with alanine substituted analogs of hACfH(1-24) at amino acid positions F-7 or W-9 completely blocked stimulation of the transfected cells. Similarly, incubation of cMC2R/cMRAP1 transfected cells with an analog of hACfH(1-24) with alanine substitutions at amino acid positions (RRP19)-R-17-P-18 resulted in a 276 fold shift in EC50 value relative to the positive control (p %26lt; 0.004). Collectively these observations suggest that cMC2R has binding sites for the HFRW motif and KICRRP motif of hACTH(1-24), and both motifs are required for full activation of the receptor. While previous studies had shown that Anolis carolinensis MC2R and Xeno pus tropicalis MC2R could be functionally expressed in CHO cells that co-expressed mouse MRAP1, co-expression of these non-mammalian tetrapod MC2Rs with cMRAP1 resulted in a significant increase in sensitivity to hACfH(1-24), as measured by EC50 value, for A. carolinensis MC2R (p %26lt; 0.005) and X. tropicalis MC2R (p %26lt; 0.007). The implications of these observations are discussed.

• 出版日期2014-9-1