Differential effects of short-acting beta2-agonists on human granulocyte functions.
BACKGROUND
beta2-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting beta2-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells.


METHODS
We examined whether widely used short-acting beta2-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O2-) production and degranulation.


RESULTS
Procaterol (PC), a full agonist, significantly inhibited both O2- production by granulocytes (neutrophils and eosinophils) and their degranulation at the clinically relevant concentrations, whereas salbutamol and tulobuterol (partial agonists) showed smaller effects. PC inhibited N-formyl methionyl-leucyl-phenylalanine-induced O2- production and peroxidase release, but failed to inhibit responses induced by phorbol 12-myristate 13-acetate and/or opsonized zymosan. Exposure to 5 x 10(-8)M PC for 120 min resulted in approximately 50% inhibition of O2- production and degranulation of neutrophils. The effects of beta2-agonists were more obvious in neutrophils than in eosinophils. A selective beta2-receptor antagonist, ICI-118551, reversed the inhibitory effect of beta2-agonists (PC, salbutamol, tulobuterol B) on N-formyl methionyl-leucyl-phenylalanine-induced O2- production.


CONCLUSIONS
These results suggest that beta2-agonists had an inhibitory effect on granulocyte functions, mainly mediated viareceptors and their efficacy. Our observations support that beta2-agonists with a rapid onset of action and high intrinsic efficacy (short-acting and full agonists) may be optimal for the rescue therapy against acute asthma attack and sedation of its airway inflammation in an early phase.
Yasui
Kozo
K
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Kobayashi
Norimoto
N
Yamazaki
Takashi
T
Agematsu
Kazunaga
K
Matsuzaki
Satoshi
S
Nakata
Setsuko
S
Baba
Atsushi
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D003864:Depression, Chemical; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006098:Granulocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000037:antagonists & inhibitors; D017265:Procaterol / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D013481:Superoxides; C010809:tulobuterol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D013726:Terbutaline; D000420:Albuterol; D017265:Procaterol