New evidence for transmitter role of VIP in the airways: impaired relaxation by a catalytic antibody.
Pulm Pharmacol Ther
; 15(2): 121-7, 2002.
Article
in En
| MEDLINE
| ID: mdl-12090785
ABSTRACT
The identity of the transmitter(s) of nonadrenergic, noncholinergic airway smooth muscle relaxation has long been investigated. Recently, nitric oxide (NO) has been proposed as the main, if not the only transmitter. We earlier suggested vasoactive intestinal peptide (VIP) as a candidate transmitter and target for pathogenic catalytic autoantibodies (VIPases) found in certain humans. To re-examine the role of VIP, we studied the airway transport and effects of a model monoclonal antibody (Ab) capable of binding and cleaving VIP. In vitro receptor binding assays indicated the catalytic light chain subunit of the VIPase Ab to inhibit the saturable binding of (Tyr(10-125)I) VIP by guinea pig lung membranes, whereas a catalytically deficient mutant of the Ab light chain was without significant inhibitory activity. Systemically administered IgG preparations of the VIPase Ab accumulated in the airway lavage fluid of guinea pigs at levels close to those in blood, suggesting that the Ab reaches the airways freely. Electrical field stimulation (EFS)-induced relaxations of tracheal strips were weaker and shorter in VIPase-treated animals than in control nonimmune IgG-treated animals. The inhibitory effect of the VIPase was dose-dependent. VIPase-mediated inhibition of EFS-induced relaxation was evident both in the absence and presence of blockade of beta-adrenergic and cholinergic receptors. Thus, circulating VIP binding and cleaving antibodies can reach the airways and attenuate the neurogenic relaxation of guinea pig tracheal smooth muscle, probably by neutralizing endogenously released VIP. The findings support a role for VIP as a major mediator of neurogenic relaxation of guinea pig tracheal smooth muscle. Lack of complete abrogation of relaxation is consistent with a co-transmitter role for NO.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vasodilator Agents
/
Vasoactive Intestinal Peptide
/
Antibodies, Catalytic
/
Muscle, Smooth
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Pulm Pharmacol Ther
Journal subject:
FARMACOLOGIA
Year:
2002
Document type:
Article
Affiliation country:
United States