[The response of the airways in asthmatic patients to kinin inhalations define a type-B2 receptor profile].
Kinins (i.e. bradykinin, kallidin and [desArg9]-bradykinin) are vasoactive oligopeptides which may contribute as mediators in the pathogenesis of asthma by interacting with specific receptors designated as B1 and B2. The aim of the present study was to investigate the airway response to inhaled histamine, bradykinin, kallidin and [desArg9]-bradykinin in normal and asthmatic subjects. Changes in airway caliber were followed as FEV1 (forced expiratory volume in 1 sec) and as Vp30 (maximum expiratory flow at 30% of the vital capacity). Neither histamine, bradykinin, kallidin nor [desArg9]-bradykinin had any measurable bronchoconstrictor effect in the normal subjects. However, in the asthmatic subjects, histamine, bradykinin and kallidin, but not [desArg9]-bradykinin, produced prompt concentration-related bronchoconstriction. The geometric mean PC20FEV1 (provocation-concentration of inhaled agonist reducing the FEV1 by 20% from baseline) values were 0.027, 0.082 and 0.44 mg/mL for bradykinin, kallidin and histamine respectively. Because bradykinin and kallidin are agonists of B2 receptors and [desArg9]-bradykinin is an agonist for B1 receptors, our data suggest that asthmatic, but not normal, airways are hyperresponsive to kinins and that this potent bronchoconstrictor response is due to a specific pharmacologic effect compatible with the stimulation of B2 receptors.
Polosa
R
R
Department of Immunopharmacology, Southampton General Hospital, Gran Bretagna.
Cacciola
R R
RR
Holgate
S T
ST
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000453:epidemiology / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007705:Kinins / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values
D007705:Kinins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter
La risposta delle vie aeree di pazienti asmatici ad inalazioni di chinine definisce un profilo recettoriale di tipo B2.