VASOPRESSIN AND VASOPRESSIN-RECEPTOR IMMUNOREACTIVITY IN SMALL-CELL LUNG-CARCINOMA (SCCL) CELL-LINES - DISRUPTION IN THE ACTIVATION CASCADE OF V-1A-RECEPTORS IN VARIANT SCCL

Four classical and three variant small-cell carcinoma of the lung (SCCL) cell lines were examined for vasopressin and vasopressin V-1a-receptor immunoreactivity. One of these classical cell lines, NCI-H345, and one variant cell line, NCI-H82, were further investigated for binding of V-1 and V-2 vasopressin-receptor antagonists, vasopressin-induced calcium mobilization, and vasopressin-induced thymidine uptake. All classical and variant SCCL cell lines examined contained vasopressin and vasopressin-receptors as determined by immunocytochemistry. Both NCI-H82 and NCI-H345 demonstrated similar binding patterns with the V-1 and V-2 vasopressin-receptor antagonists, indicating the presence of both receptor subtypes. For the classical cell line (NCI-H345), vasopressin (1 mu M) induced an increase in cytosolic free calcium, while the peptide was ineffective at increasing cytosolic calcium in the variant cell line (NCI-H82). However, vasopressin (0.1 or 1 mu M) was unable to stimulate thymidine uptake in the classical (NCI-H345) or variant (NCI-H82) cell lines for the conditions used. These results indicate that both classical and variant SCCL produce vasopressin, and vasopressin V-1a and V-2 receptors. In the variant cell line, there appears to be a disruption in the activation cascade for cV(1a) receptors as indicated by the lack of vasopressin-induced calcium mobilization.