Pharmacologic properties of brewery dust extracts in vitro.
OBJECTIVE
To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro.


METHODS
Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal.


METHODS
Mount Sinai School of Medicine, Department of Pulmonary Medicine.


METHODS
The isolated guinea pig tracheal tissue of 18 guinea pigs.


METHODS
Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts.


RESULTS
The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract.


CONCLUSIONS
We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic receptors. This effect is not dependent on presensitization of the guinea pigs.
Schachter
E N
EN
Mount Sinai School of Medicine, New York, NY 10029-6574, USA. NSCHACHTER@SMTPLINK.MSSM.EDU
Zuskin
E
E
Rienzi
N
N
Goswami
S
S
Castranova
V
V
Whitmer
M
M
Siegel
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004391:Dust; D002523:Edible Grain; D004731:Endotoxins / Q000032:analysis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000032:analysis / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*
D004391:Dust; D004731:Endotoxins; D011950:Receptors, Cholinergic; D009240:N-Formylmethionine Leucyl-Phenylalanine