Degradation of vasoactive intestinal peptide by isolated, ventilated, and perfused rat lungs

The degradation of vasoactive intestinal peptide (VIP) was studied using an isolated perfused rat lung model. 125iodine labelled VIP (125I-VIP) was used as a tracer. VIP was cleared from the perfusate by a single lung passage up to concentrations of 1 nmol l-1. The clearance rate was decreased at higher concentrations of VIP. VIP was taken up by the lung tissue and the cleavage products were re-extruded into the perfusate. The time delay of re-extrusion was increased at starting concentrations of VIP exceeding 1 nmol l-1 and in the presence of the lysosomal inhibitor chloroquine. After a bolus of 9 pmol or 40 nmol 125I-VIP into the pulmonary artery catheter 6.3 pmol or 2920 pmol, respectively, were bound by the lung. Most of the radioactive material was extruded within 25 min and consisted of low molecular weight 125I-labelled degradation products. We conclude that the receptors for VIP in the alveolar capillaries are of high affinity and capacity to extract VIP from the circulation and that lysosomes may be involved in the degradation. The degradation products are of low molecular weight.