1. Evidence for multiple rat VPAC1 receptor states with different affinities for agonists
- Author
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Magali Waelbroeck, Rebeca Busto, Salvatore De Maria, Patrick Robberecht, and Ma-Guillerma Juarranz
- Subjects
Agonist ,GTP' ,G protein ,medicine.drug_class ,Receptors, Vasoactive Intestinal Polypeptide, Type I ,Chinese hamster ovary cell ,Cholera toxin ,Cell Biology ,CHO Cells ,Guanosine triphosphate ,medicine.disease_cause ,Peptides, Cyclic ,Rats ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Cricetinae ,medicine ,Animals ,Receptors, Vasoactive Intestinal Peptide ,Guanosine Triphosphate ,Receptor ,Ternary complex ,Vasoactive Intestinal Peptide - Abstract
We compare the binding properties of [125I-VIP] and [125I]-Ro 25 1553 to VPAC1 receptors, expressed in stably transfected CHO cells. [125I]-VIP labelled two VPAC1 receptor states, while [125I]-Ro 25 1553 labelled selectively a limited number of high-affinity receptors. This high-affinity state probably corresponds to an agonist-receptor-Gs ternary complex as its properties (guanyl nucleotides, EC50 values and maximal effect) were affected by cholera toxin pre-treatment. Both high- and low-affinity receptors participated in the adenylate cyclase activation. This suggested that agonists activate not only low-affinity uncoupled receptors by facilitating the ternary complex formation, but also activated the high-affinity ternary complex by accelerating the GTP binding to emptied, receptor-bound G proteins.
- Published
- 1999