Structural and pharmacological differences between codfish and rat brain alpha 1-adrenergic receptors revealed by photoaffinity labeling with 125I-APDQ.
The photoaffinity probe 125I-APDQ has been used to characterize alpha 1-receptor peptides in the cod and rat brains. In the cod brain a major specific peptide of Mr = 68,000 could be covalently labeled by 125I-APDQ as revealed by SDS-PAGE. In the rat brain a specific peptide with Mr = 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 alpha 1-receptors in both species. The ligand binding peptide in the cod brain also distinguished between stereoisomers of epinephrine as expected for a physiological receptor. However, there was a distinct difference between the cod and rat alpha 1-receptor in that the beta-agonist 1-isoprenaline was equipotent to 1-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 alpha 1-adrenergic ligand 3H-prazosin from alpha 1-receptor binding sites in brain membranes from both species. Thus, the codfish alpha 1-receptor seems to be different from mammalian alpha 1-receptors both structurally and pharmacologically.
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005399:Fishes; D007545:Isoproterenol / Q000378:metabolism; D008970:Molecular Weight; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013045:Species Specificity; D013237:Stereoisomerism
D000345:Affinity Labels; D001386:Azides; D011942:Receptors, Adrenergic, alpha; C039335:4-amino-6,7-dimethoxy-2-(4-(5-(3-iodo-4-azidophenyl)pentanoyl)-1-piperazinyl)quinazoline; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin