Beta-adrenergic regulation of secretion in Clara cell adenomas of the mouse lung

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6936563

Palmer, K C; Grammas, P

Certain chemically-induced pulmonary adenomas of the mouse have been characterized as being Clara cell in origin. In examining these Clara cell tumors as a model of normal Clara cell biology, they studied the response of tumor cells in vivo to the secretory agonist, isoproterenol (10 mg/kg) and the antagonist propranolol (2.0 mg/kg) 1 hr. following intraperitoneal injection of 120 day old tumor-bearing mice. Ultrastructural morphometry was used to quantitate the secretory response of tumor cells by measuring the volume density of the secretory granules. In the intact animal, isoproterenol stimulated secretion in the Clara cell adenomas (40% decrease in vol. dens. with no change in surface to volume ratio of granules) while propranolol prevented this effect. Beta-adrenergic receptors on isolated tumor Clara cells were demonstrated by radioligand binding assay using /sup 125/I-iodocyanopindolol (ICYP). Scatchard analysis of data derived from whole cells indicates a maximum receptor binding capacity of 27 fmol/mg protein and a K/sub D/ of 0.029 nM. Isoproterenol displacement of ICYP binding yields an IC/sub 50/ of 8 x 10/sup -7/M and a calculated K/sub D/ of 3.36 x 10/sup -7/M. The beta/sub 2/ identity of these receptors was determined utilizing the relatively specific beta/sub 1/ and beta/sub 2/ antagonists practolol and ICI-118,551, respectively. Practolol failed to displace more than 30% of ICYP binding even at 100 ..mu..M, while ICI-118,551 displacement of ICYP yielded a linear (r = 0.93) Hofstee plot and a K/sub D/ of 5.04 x 10/sup -9/M. These findings suggest that the secretory activity of adenoma-derived Clara cells is under beta-adrenergic control similar to that of normal bronchiolar Clara cells.

• Research Organization: Wayne State Univ. School of Medicine, Detroit, MI
• OSTI ID: 6936563
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOMAS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LUNGS
MAMMALS
MEMBRANE PROTEINS
MICE
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RESPIRATORY SYSTEM
RODENTS
SECRETION
SYMPATHOMIMETICS
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES