1 In this study we have characterized the receptor(s) in the rat mesenteric artery mediating relaxant responses to adenosine and a number of adenosine analogues, N 6 -R-phenylisopropyladenosine (R-PIA), N 6 -cyclopentyladenosine (CPA) . We have also studied the e ects of endothelial removal and uptake inhibition by nitrobenzylthioinosine (NBTI) and the e ects of the A 3 receptor antagonist 1,3-dipropyl-8-(4-acrylate)phenylxanthine (BWA1433). 2 Adenosine, NECA, CPA and R-PIA all elicited relaxant responses in tissues precontracted with phenylephrine (1 mM) with the following potency order: NECA4R-PIA4adenosine=CPA. However, E/[A] curves to NECA were biphasic. CGS 21680 was inactive at concentrations up to 30 mM and IB-MECA elicited relaxant responses which were resistant to blockade by 8-SPT and BWA1433 (100 mM). 3 Removal of the endothelium produced a small but signi®cant decrease in the asymptote of the high potency phase of E/[A] curves to NECA with no change in p[A] 50 . E/[A] curves to adenosine were not altered by removal of the endothelium. However, there were small rightward shifts of E/[A] curves to CPA and R-PIA in the absence of endothelium. 4 Inhibition of uptake by NBTI (1 mM) had no e ect on E/[A] curves to NECA, CPA or R-PIA, but E/[A] curves to adenosine were signi®cantly left-shifted in the presence of NBTI. 5 8-SPT (10 ± 100 mM) caused signi®cant rightward shifts of the high potency phase of the E/[A] curves to NECA (pA 2 =5.63+0.26). The second phase of the concentration-response curve to NECA appeared to be resistant to blockade by 8-SPT, as were E/[A] curves for adenosine, CPA or R-PIA. However, in the presence of NBTI (1 mM), 8-SPT (100 mM) gave signi®cant rightward shifts of E/[A] curves to adenosine. 6 ZM 241385 (0.1 ± 1 mM) produced signi®cant rightward shifts of the high potency phase of NECA E/[A] curves (pA 2 =7.65+0.25 in the presence and 7.20+0.12 in the absence of endothelium), while curves to R-PIA were not signi®cantly shifted by 1 mM ZM 241385. In the presence of NBTI E/[A] curves to adenosine were signi®cantly rightward shifted by ZM 241385 (0.1 mM, pA 2 =7.50+0.16). 7 In conclusion, the results suggest activation of A 2B receptors located primarily on the smooth muscle by low concentrations of NECA and by adenosine under conditions of uptake blockade, and of another, as yet unde®ned site which may be intracellular, by higher concentrations of NECA, by CPA, R-PIA and adenosine under conditions where uptake is operational.,

A total of 261 patients with symptomatic, mild to moderate asthma were randomized to treatment in this 4-week, double-blind, parallel-group comparison of fluticasone propionate 200 micrograms/d with beclomethasone dipropionate 400 micrograms/d. Improvements from both treatments were seen in diary card data. Morning peak expiratory flow rate (PEFR) improved from 375 to 390 and 371 to 382 l/min with fluticasone propionate and beclomethasone dipropionate, respectively. Symptom scores, percentage of symptom-free days and nights, and use of rescue beta 2-agonist medication also improved, as did clinical lung function. With the exception of percentage of rescue-free days, which was greater for beclomethasone dipropionate, none of the differences between the groups were statistically significant. There was a significant difference between treatments in the number of rescue-free days over days 1-28; however, there was no difference between treatments in the number of rescue-free days over days 1-14, nor was there any difference in the number of inhalations of rescue medication used throughout the study. Very few adverse effects were reported. Although all mean plasma cortisol values were within the normal range, they were significantly different between treatments, rising from 402 to 429 nmol/l with fluticasone propionate, and falling from 435 to 394 nmol/l with beclomethasone dipropionate (P = 0.006). Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate (P = 0.024). In conclusion, fluticasone propionate 200 micrograms/d is as effective as beclomethasone dipropionate 400 micrograms/d with less effect on plasma cortisol levels.

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)