Evidence for multiple rat VPAC1 receptor states with different affinities for agonists.
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.
Busto
R
R
Departmento de Bioquímica y Biología Molecular, Universidad de Alcalà, Madrid, Spain.
Juarranz
M G
MG
De Maria
S
S
Robberecht
P
P
Waelbroeck
M
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006160:Guanosine Triphosphate / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism*; D051381:Rats; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000378:metabolism
D010456:Peptides, Cyclic; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide; D006160:Guanosine Triphosphate