title: Evidence that toluene diisocyanate activates the efferent function of capsaicin-sensitive primary afferents.
abstract: Isocyanates are an important cause of occupational asthma. The mechanism of isocyanate-induced asthma is still unknown. To determine whether toluene diisocyanate stimulates the 'efferent' function of peripheral endings of capsaicin-sensitive sensory nerves, we investigated the effect of toluene diisocyanate in the rat isolated urinary bladder, a preparation in which the action of capsaicin has been well characterized. Toluene diisocyanate (0.03-3 mM) produced a concentration-dependent contraction of the bladder strips. Its maximal effect was about 50% of the response to capsaicin (1 microM). Previous exposure of the strips to capsaicin followed by washing out produced complete unresponsiveness, both to the first exposure to toluene diisocyanate and to a second exposure of capsaicin. Further, the response to both toluene diisocyanate and capsaicin was completely prevented by extrinsic bladder denervation, achieved by bilateral removal of pelvic ganglia (72 h before). Repeated exposure of the rat bladder to toluene diisocyanate reduced the capsaicin-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as biochemical marker of activation of these sensory nerves. These experiments provide the first evidence that toluene diisocyanate activates directly or indirectly the efferent function of capsaicin-sensitive primary sensory nerves.
authors.affiliation: Institute of Occupational Medicine, University of Padua, Italy.
authors.forename: C E
authors.initials: CE
authors.lastname: Mapp
authors.forename: P
authors.initials: P
authors.lastname: Chitano
authors.forename: L M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: R
authors.initials: R
authors.lastname: Patacchini
authors.forename: P
authors.initials: P
authors.lastname: Santicioli
authors.forename: P
authors.initials: P
authors.lastname: Geppetti
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D003485:Cyanates / Q000494:pharmacology*; D004558:Electric Stimulation; D005725:Ganglia, Autonomic / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009121:Muscle Denervation; D009476:Neurons, Efferent / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation
chemical_list: D003485:Cyanates; D014051:Toluene 2,4-Diisocyanate; C026942:2,6-diisocyanatotoluene; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin