Inhibition of ACTH Release by Peptide Hormones: Molecular Mechanisms and PossibleRole as Anti-Stress Factors

摘要

The major objectives of this proposal were to investigate the biochemicalproperties of somatostatin (SRIF) receptors. We were able to solubilize the receptor in an active form and have shown using immunoprecipitation procedures that the receptor is coupled to subtypes of Gi and Go. The receptor contains sialic acid residues involved in promoting agonist binding. We have developed antibodies against the receptor. The antibodies selectively recognize the receptor by immunoblotting and can specifically immunoprecipitate the receptor from AtT-20 cells. The antibodies are being used to further investigate the physical properties of the receptor and to clone cDNA encoding the receptor from an expression library generated from AtT-20 cells. We have shown that subtypes of SRIF receptors exist and have developed selective agonists at each receptor subtype. The receptors have different distributions in brain, have distinct pharmacological and biochemical characteristics, can be differentially regulated and mediate distinct physiological actions of SRIF in brain and peripheral tissues. Attempts are underway to identify the physical basis for the functional differences in these receptor subtypes.