Characterization and localization of vasoactive intestinal peptide receptors in the rat lung.

Experiments were performed to characterize vasoactive intestinal peptide (VIP) receptors in rat lung and to study their localization by means of light and electron microscope autoradiography. [125I]Iodo-VIP binding to lung homogenate was inhibited by synthetic VIP, [Val5]secretin, secretin, and 7-27 secretin with half-maximal inhibition (ID50) values of 1.62, 13, 121 nmol/liter and up to 0.1 mmol/liter, respectively. The relative potency of [Val5]secretin and 7-27 secretin to displace the tracer indicated that [125I]iodo-VIP binds to specific VIP receptors. Kinetic studies showed two sites of binding, a site of high affinity with equilibrium dissociation constant (KD) values of 0.32 +/- 0.09 nM and Bmax of 88.7 +/- 28.6 fmol/mg protein and a lower affinity binding site with a KD value of 23.0 +/- 2.9 mM and Bmax of 584 +/- 136.9 fmol/mg protein. The localization of VIP receptors was performed by radioautography both in vivo after iv injection of [125I]iodo-VIP and in vitro by the direct application of the radiolabeled peptide to cryostat sections of unfixed lung tissue. After iv injection of label, silver grains were detected only over alveoli. Electron microscopy indicated that radioactivity was mostly associated with alveolar capillaries. In vitro localization studies showed specific binding not only to alveoli but also to bronchi. These studies suggest that VIP can act at different sites and that the peptide could gain access to alveoli via the general circulation.