Vasopressin and vasopressin-receptor immunoreactivity in small-cell lung carcinoma (SCCL) cell lines: disruption in the activation cascade of V1a-receptors in variant SCCL.
Four classical and three variant small-cell carcinoma of the lung (SCCL) cell lines were examined for vasopressin and vasopressin V1a-receptor immunoreactivity. One of these classical cell lines, NCI-H345, and one variant cell line, NCI-H82, were further investigated for binding of V1 and V2 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 V1 and V2 vasopressin-receptor antagonists, indicating the presence of both receptor subtypes. For the classical cell line (NCI-H345), vasopressin (1 microM) 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 microM) 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 V1a and V2 receptors. In the variant cell line, there appears to be a disruption in the activation cascade for V1a receptors as indicated by the lack of vasopressin-induced calcium mobilization.
Fay
M J
MJ
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756.
Friedmann
A S
AS
Yu
X M
XM
North
W G
WG
D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000096:biosynthesis*; D013936:Thymidine / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D014667:Vasopressins / Q000096:biosynthesis*
D017483:Receptors, Vasopressin; D014667:Vasopressins; D000001:Calcimycin; C033170:4-bromo-A-23187; D002118:Calcium; D013936:Thymidine