Effects of thiazinamium chloride on surfactant production in primary cultures of type II cells isolated from adult rat lung

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5233441

Gilfillan, A M; Lewis, A J; Rooney, S A

Thiazinamium-Cl (T), an analog of promethazine (P), has antiasthmatic activity that may be related to its antihistaminic and anticholinergic actions or its ability to inhibition thromboxane synthesis. To assess phosphatidylcholine (PC) secretion, freshly isolated cells were preincubated with /sup 3/H-choline for 18 h and then incubated in fresh medium +/- test agent for 90 min when /sup 3/H-PC in the cells and medium was measured. PC synthesis was similarly assessed during the latter incubation period by measuring the rate of /sup 3/H-choline incorporation into cellular PC. 10/sup -6/ M T stimulated PC secretion by 46% from 0.92 +/- 0.05 (PC in the medium as % of total) to 1.34 +/- 0.08 (P < 0.01, n = 6). The EC/sub 50/ was 2.9 x 10/sup -8/ M. In comparison, terbutaline (Tb) maximally stimulated PC secretion by 108% at 10/sup -5/ M (P < 0.001, n = 13) and isoproterenol (I) by 112% at 10/sup -7/ M (P < 0.01, n = 5). The EC/sub 50/ values for Tb and I were 1.6 x 10/sup -7/ M and 3.2 x 10/sup -9/ M, respectively. T did not stimulate PC synthesis nor increase lactate dehydrogenase release. Thus, the effect on secretion was not due to increased synthesis or to cell injury. The effect of T on PC secretion was mimicked by 10/sup -6/M P (48% stimulation, P < 0.01, n = 7) and by 10/sup -5/M pyrilamine, a structurally dissimilar antihistamine, (52% stimulation, P < 0.002, n = 7). The effects of T or pyrilamine and of Tb were additive suggesting a different mechanism of action. Although histamine did not inhibit PC secretion it may play a physiologic role in its regulation.

• Research Organization: Yale Univ, New Haven, CT
• OSTI ID: 5233441
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
ANTIHISTAMINICS
AZOLES
BIOLOGICAL EFFECTS
CELL CULTURES
CHOLINE
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
HISTAMINE
HYDROXY COMPOUNDS
IMIDAZOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
QUATERNARY COMPOUNDS
RATS
RODENTS
SECRETION
SURFACTANTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES