Monkey corticotropin-releasing factor1 receptor: Complementary DNA cloning and pharmacological characterization

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• The corticotropin-releasing factor type 1 (CRF1) receptor plays a crucial role in the stress response.
• Understanding the molecular and pharmacological properties of primate CRF1 receptors is essential for comparative studies and drug development.

Purpose of the Study:

• To isolate and characterize the complementary DNA (cDNA) of the rhesus monkey CRF1 receptor.
• To investigate the binding affinities and signaling pathways of the monkey CRF1 receptor.

Main Methods:

• Isolation of monkey CRF1 receptor cDNA from a rhesus monkey amygdala library.
• Expression of the receptor in COS-7 cells for binding assays with radiolabeled ovine CRF.
• Testing the effects of CRF and CRF-related peptides, receptor antagonists, and GTP analogs on receptor binding and cyclic AMP formation.

Main Results:

• The monkey CRF1 receptor cDNA encodes a 415-amino acid protein with 99.5% sequence identity to the human CRF1 receptor.
• Expressed monkey CRF1 receptor exhibited specific binding to [125I]-ovine CRF, inhibited by CRF, related peptides, and antagonists.
• GTP analogs indicated G-protein coupling, and activation led to increased cyclic AMP, consistent with G-protein coupled receptor (GPCR) function.

Conclusions:

• The monkey CRF1 receptor possesses similar molecular and pharmacological characteristics to its human counterpart.
• These findings support the conserved role of CRF1 receptors in stress regulation across primate species.
• The characterized monkey CRF1 receptor serves as a valuable model for studying stress-related disorders and evaluating CRF1 antagonists.