Evidence for Multiple Rat VPAC 1 Receptor States with Different Affinities for Agonists

Abstract

We compare the binding properties of [ 125I-VIP] and [ 125I]-Ro 25 1553 to VPAC 1 receptors, expressed in stably transfected CHO cells. [ 125I]-VIP labelled two VPAC 1 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-G s ternary complex as its properties (guanyl nucleotides, EC 50 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.