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Br J Pharmacol. 1998 Oct;125(4):717-26.

Influence of receptor number on the stimulation by salmeterol of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor.

Author information

1
Institute of Cell Signalling and School of Biomedical Sciences, Medical School, Queen's Medical Centre, Nottingham.

Abstract

1. The beta2-agonist salmeterol is a potent relaxant of airway smooth muscle with a long duration of action. Previous studies of cyclic AMP accumulation, however, have indicated that salmeterol is a low efficacy beta2-agonist when compared to isoprenaline. Here we have compared the properties of salmeterol and isoprenaline as stimulants of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor to different levels (50 and 310 fmol mg protein(-1)). 2. Gene transcription was monitored using a secreted placental alkaline phosphate (SPAP) reporter gene under the transcriptional control of six cyclic AMP response element (CRE) sequences. 3. In the lower expressing cells (CHO-beta2/6), salmeterol produced a maximal cyclic AMP response that was only 22% that of that obtained with isoprenaline. In contrast in the higher expressing cells (CHO-beta2/ 4), the two maxima were of similar magnitude. 4. Salmeterol was a more potent stimulant of gene transcription, producing the same maximal response as isoprenaline in both cell lines. Furthermore, in the CHO-beta2/4 cells, Salmeterol was 50 fold more potent as a stimulant of SPAP secretion than of cyclic AMP accumulation. In contrast, isoprenaline was 24 fold less sensitive as a stimulant of SPAP secretion than of cyclic AMP accumulation. In the presence of serum (10%), the effects of both salmeterol and isoprenaline on gene transcription were augmented. 5. These data suggest that the low efficacy and/or long duration of action of salmeterol, favours a potent stimulation of gene transcription when compared to more efficacious but shorter-lived agonists such as isoprenaline.

PMID:
9831907
PMCID:
PMC1571039
DOI:
10.1038/sj.bjp.0702139
[Indexed for MEDLINE]
Free PMC Article

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