Pharmacologic effects of tobacco dust extract on isolated Guinea pig trachea.
OBJECTIVE
To determine the effects of tobacco dust extract (TDE) on isolated guinea pig tracheal smooth muscle.


METHODS
A controlled, in vitro smooth-muscle study of the effect of pharmacologic agents on TDE.


METHODS
The effect of TDE on isolated guinea pig tracheal smooth muscle was tested using water-soluble extracts of dust obtained from machines in a cigarette manufacturing plant. Dose-related contractions of nonsensitized guinea pig trachea were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin). Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth-muscle contraction: atropine, indomethacin, pyrilamine, nordihydroguaretic acid, acivicin, bromophenacyl bromide, 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester, captopril, and capsaicin.


RESULTS
Atropine strikingly reduced the contractile effects of these extracts. Inhibition of contraction by blocking other mediators was less complete. There was no inhibition of contraction by hexamethonium (10(-4) mol/L, 10(-5) mol/L, 10(-6) mol/L), suggesting that nicotine was not the major contractile mediator of TDE. A separate analysis using different molecular weight fractions of TDE indicated that the constrictor activity appears to be primarily in the fraction with a molecular weight < 10 kd. Additionally, the constrictor effect resided entirely in the nonlipid fraction of the extract. We suggest that TDE causes dose-related airway smooth-muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and possibly cholinergic receptors.


CONCLUSIONS
The bronchoconstrictor activity of TDE resides primarily in its low molecular weight, nonlipid fraction, and hexamethonium studies suggest that this agent is not nicotine.
Schachter
E Neil
EN
Mount Sinai Hospital, New York, NY 10029, USA. NeilSchachter@MSSM.EDU
Zuskin
Eugenija
E
Goswami
Satindra
S
Castranova
Vincent
V
Siegel
Paul
P
Whitmer
Mike
M
Gadgil
Aneal
A
D000395:Air Pollutants, Occupational / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004391:Dust / Q000032:analysis; D004731:Endotoxins / Q000032:analysis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010936:Plant Extracts / Q000032:analysis / Q000633:toxicity*; D014026:Nicotiana / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects*
D000395:Air Pollutants, Occupational; D004391:Dust; D004731:Endotoxins; D010936:Plant Extracts; D001285:Atropine