An inverse relationship between receptor internalization and the fraction of laterally mobile receptors for the vasopressin renal-type V2-receptor. An active role for receptor immobilization in down-regulation?

Lateral mobility of the vasopressin renal-type V₂-receptor was investigated in LLC-PK₁, porcine epithelial cells using the technique of fluorescence microphotolysis (photobleaching) and a rhodamine-labelled vasopressin analogue. At various times after ligand addition, cells were analyzed for both receptor lateral mobility and ligand internalization. The V₂-receptor mobile fraction diminished from 0.9 to 0.43 over 60 min at 37°C. whereas the apparent lateral diffusion coefficient remained essentially unchanged (2-3 × 10^-10 cm² s). Interestingly, the fraction of immobile V₂-receptors corresponded exactly with the fraction of internalized receptors, implying a functional relationship. These observations together with comparable results reported for other polypeptide hormone receptors indicate a possible machanistic role for receptor immobilization in the desensitization of hormonal response.