Species differences in the molecular characteristics of vasoactive‐intestinal‐peptide receptors in the pancreas from rat and guinea‐pig

Abstract

1 The receptors for vasoactive intestinal peptide (VIP) present in dispersed acini and membranes from rat and guinea-pig pancreas differed in selectivity pattern, i.e. in the displacement of [¹²⁵I]iodo-VIP by parent peptides, as revealed by a VIP:secretin IC₅₀ ratio at least ten times higher in rat than in guinea-pig preparations. The molecular properties of these VIP receptors were therefore investigated. 2 When comparing six succinimidyl ester cross-linkers, bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone proved to be the most universal [¹²⁵I]iodo-VIP cross-linker for all pancreatic preparations. 3 In intact rat acini the main labeled peptide had an M_r of 80000, whereas the main labeled peptide in intact guinea-pig acini was a smear of M_r 160000. In both rat and guinea-pig pancreatic membranes, the main labeled peptide ([¹²⁵I]iodo-VIP–binding-protein complex) had an M_r of 66000. In addition, variable proportions of an M_r-80000 peptide and an M_r-83000 peptide were visualized in, respectively, rat and guinea-pig membranes. The labeling of all peptides was suppressed by VIP and by GTP. Reducing conditions allowed only a better resolution, making the presence of intermolecular disulfide bridges unlikely. 4 Taking into account the M_r of VIP it is thus plausible that the main native M_r-77000 VIP-binding site present in rat acini could be easily converted to an M_r-63000 peptide during membrane preparation, while in guinea-pig acini M_r-80000 and/or M_r-63000 VIP-binding sites were often closely associated with another membrane component in the native state. These molecular differences between VIP receptors in intact rat and guinea-pig acini are in keeping with functional differences.