STRUCTURAL CHARACTERIZATION OF PACAP RECEPTORS ON RAT-LIVER PLASMA-MEMBRANES

Pituitary adenylate cyclase-activating polypepiide-38 (PACAP-38) and P ACAP-27 are recently characterized hypothalamic peptides with marked h omology with vasoactive intestinal peptide (VIP), which are concentrat ed in the innervation of the digestive tract. We now report that, on r at liver plasma membranes, PACAP interacts with at least two types of receptors: receptors demonstrating equally high affinity for PACAP and VIP and receptors with high affinity for PACAP but low affinity for V IP. In contrast, on rat intestinal epithelial cell laterobasal membran es, only receptors with high affinities for PACAP and VIP were observe d. After I-125-labeled VIP or I-125-labeled PACAP-27 was cross-linked to the liver plasma membrane receptors with the use of either disuccin imidosuberate or disuccinimido dithiobis(propionate), analysis of the resulting ligand-receptor complexes on sodium dodecyl sulfate-polyacry lamide gel electrophoresis showed that the structures of the VIP and P ACAP receptors were similar: both ligand-receptor complexes displayed two radioactive bands with relative molecular weights of 80,000 and 56 ,000 under reducing conditions and of 75,000 and 53,000 under nonreduc ing conditions. These findings suggest that the receptors for the PACA P peptides and VIP are closely related, reflecting the marked homology between these peptides. The presence of receptors specific for PACAP on rat liver plasma membranes should stimulate further studies of the interaction between PACAP and the liver.