Structural and pharmacological differences between codfish and rat brain α1-adrenergic receptors revealed by photoaffinity labeling with 125I-APDQ

The photoaffinity probe 125I-APDQ has been used to characterize α1-receptor peptides in the cod and rat brains. In the cod brain a major specific peptide of Msub(r)=68,000 could be covalently labeled by 125I-APDQ as revealed by SDS-PAGE. In the rat brain a specific peptide with Msub(r)=77,000 was instead labeled. When a number of adrenergic agonists and antagonists were tested for their ability to protect the labeling by 125I-APDQ their potencies were those expected for α1-receptors in both species. The ligand binding peptide in the cod brain also distinguished between stereoisomers if epinephrine as expected for a physiological receptor. However, there was a distinct difference between the cod and rat α1-receptor in that the β-agonist l-isoprenaline was equipotent to l-norepinephrine in the cod whereas it was less potent in the rat. The protecting ability of the tested agents were also matched by their ability to displace the α1-adrenergic ligand 3H-prazosin from α1-receptor binding sites in brain membranes from both species. Thus, the codfish α1-receptor seems to be different from mammalian α1-receptors both structurally and pharmacologically. (author)