Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Comparison of the effects of UTP and 5 '-AMP on guinea-pig lung function and airways mucus secretion [Abstract]

Broadley, Kenneth John ORCID:, Jackson, A. and John, Emma Alison 2010. Comparison of the effects of UTP and 5 '-AMP on guinea-pig lung function and airways mucus secretion [Abstract]. Purinergic Signalling 6 (1) , pp. 140-141. 10.1007/s11302-009-9175-x

Full text not available from this repository.


Uridine triphosphate (UTP)1 and adenosine2 stimulate P2Y2 and P1 receptors, respectively, located on lung goblet cells,their activation promoting mucus secretion. We compared inhaled UTP and 5’-AMP on mucus secretion and airways function in an in vivo mucus hypersecretory phenotype model. Male Dunkin-Hartley guinea-pigs (200–250 g) were sensitised with ovalbumin (OA 100μg) and Al(OH)3 (100 mg i.p.) on days 1 and 5. Guinea-pigs received nebulised OA (60 min 0.01%) on day 15, and 0.1% on days 17, 19, 21, 23, 25, 27 and 29, with mepyramine maleate (30 mg/kg ip) 1 hr prior to OA challenge on days 17–27. On day 30, guinea-pigs (n=6) received: nebulised UTP (1 or 10 mM/15mins); UTP 30mins following suramin hexasodium (60 mg/kg ip); 5’-AMP (3 mM for 1 min) or vehicle. Whole body plethysmography measured specific airway conductance (sGaw) before and following UTP or 5’-AMP. Guinea-pigs were then anaesthetic overdosed, lungs removed, inflated with formaldehyde (1 ml/100 g), fixed and embedded in paraffin wax. Sections (3 μm) were stained with alcian blue/periodic acid-Schiff (AB/PAS). Area of AB/PAS-stained mucin-positive epithelium was expressed as % total epithelial area measured with SigmaScan Image Analysis program. UTP (1 and 10 mM) gradually reduced sGaw, reaching −29.77±8.70 and −27.2±2.4% after 60 min. AB/PAS-positive epithelium was significantly reduced from 30.1±5.7% after vehicle to 9.5±2.0% and 16.5±2.8%, indicating mucin release, which suramin blocked. No mucin loss occurred at 0 h (24.4±4.0%) compared to vehicle (24.3±2.8%), significant reduction at 1 h (12.1±2.7%) and partial recovery at 48 h (18.9±2.7%). 5’-AMP caused no immediate changes in sGaw; OA challenges had presumably degranulated mast cells. At 5 h there was a late bronchoconstriction (peak sGaw fall −31.5±5.2%) lasting 24 h. AB/PAS-positive epithelium was significantly reduced from 47.06±3.95% to 30.5±4.2% by 5’-AMP challenge. Thus, P1 and P2Y2 receptor stimulation release mucus, the latter accompanied by airways function changes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Additional Information: 1st UK Purine Symposium, 19th November 2009
Publisher: Springer Verlag
ISSN: 1573-9538
Last Modified: 18 Oct 2022 13:47

Actions (repository staff only)

Edit Item Edit Item