PT  - JOURNAL ARTICLE
AU  - N M Muñoz
AU  - K F Rabe
AU  - A J Vita
AU  - K McAllister
AU  - D Mayer
AU  - M Weiss
AU  - A R Leff
TI  - Paradoxical blockade of beta adrenergically mediated inhibition of stimulated eosinophil secretion by salmeterol.
DP  - 1995 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 850--854
VI  - 273
IP  - 2
4099  - http://jpet.aspetjournals.org/content/273/2/850.short
4100  - http://jpet.aspetjournals.org/content/273/2/850.full
SO  - J Pharmacol Exp Ther1995 May 01; 273
AB  - Salmeterol (SALM) is a long-acting beta 2 adrenoceptor agonist that causes prolonged relaxation of airway smooth muscle. To determine whether this agent also causes prolonged inhibition of stimulated eosinophil secretion, we studied interactions between SALM and albuterol (ALB) in inhibiting eosinophil peroxidase (EPO) secretion in human eosinophils in vitro. Peripheral blood eosinophils were isolated from 18 human volunteers by negative immunoselection, and secretion of EPO was elicited with 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml cytochalasin B (CytB) in aliquots of 10(5) cells. Eosinophils were pretreated with either 10(-8) M ALB, 10(-8) M SALM or SALM + ALB for 5 min to 18 hr at 37 degrees C. Pretreatment with ALB for 5 min caused inhibition of stimulated secretion of EPO to 783 +/- 210 ng/10(6) cells vs. 1475 +/- 286 ng/10(6) cells for eosinophils not treated with ALB (P < .05; n = 5). Inhibition of EPO secretion caused by ALB was sustained for 30 min (924 +/- 160 ng/10(6) cells; P < .05 vs. fMLP + CytB; n = 5). By contrast, SALM had no inhibitory effect on fMLP-induced secretion after incubation for 5 min to 18 hr. In cells obtained from four separate isolations, pretreatment with 10(-8)M SALM before addition of ALB blocked the inhibition of EPO release caused by 10(-8)M ALB alone (486 +/- 28 ng/10(6) cells for ALB alone vs. 902 +/- 32 ng/10(6) cells for SALM + ALB; P < .01; n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)