TY - JOUR
T1 - ANP secretion from small cell lung cancer cell lines
T2 - A potential model of ANP release
AU - Wigle, D. A.
AU - Campling, B. G.
AU - Sarda, I. R.
AU - Shin, S. H.
AU - Watson, J. D.
AU - Frater, Y.
AU - Flynn, T. G.
AU - Pang, S. C.
PY - 1995
Y1 - 1995
N2 - Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of ~10-20 g · cell-1 · min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99-126) and ANP- (1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies. The two identified SCLC cell lines may provide a unique opportunity to investigate the molecular events associated with ANP secretion.
AB - Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of ~10-20 g · cell-1 · min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99-126) and ANP- (1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies. The two identified SCLC cell lines may provide a unique opportunity to investigate the molecular events associated with ANP secretion.
KW - arginine vasopressin
KW - atrial natriuretic peptide release
KW - calcium ionophore A-23187
KW - perifusion technique
KW - sodium ionophore monensin
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U2 - 10.1152/ajpheart.1995.268.5.h1869
DO - 10.1152/ajpheart.1995.268.5.h1869
M3 - Article
C2 - 7771538
AN - SCOPUS:0029025246
SN - 0363-6135
VL - 268
SP - H1869-H1874
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5 37-5
ER -