The online version of this article (doi:10.1186/1465-9921-15-29) contains supplementary material, which is available to authorized users.
Chantal Donovan, Mirjam Simoons contributed equally to this work.
The authors declare that they have no competing interests.
CD, MS, JE, JNC, MF conducted all experiments. CD, MS, JE, JNC, MF and JEB analyzed data and conceptualized project. CD, MS, JEB wrote the paper. CD, MS, JE, JNC, MF and JEB approved the submission.
Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices.
Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce β-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca2+ sensitivity in the absence of contractile agonist-induced Ca2+ oscillations. Furthermore, the effects of RGZ, CQ, ALB and isoproterenol (ISO) on the initiation and development of methacholine-induced contraction were also compared.
RGZ and CQ, but not ALB or ISO, elicited complete relaxation with increasing MCh pre-contraction and maintained their potency and efficacy following β-adrenoceptor desensitization. RGZ, CQ and ALB maintained efficacy following overnight incubation with RGZ or CQ. Relaxation responses to all dilators were generally maintained but delayed after caffeine/ryanodine. Pre-treatment with RGZ, but not CQ, ALB or ISO, reduced MCh potency.
This study demonstrates the superior effectiveness of RGZ in comparison to CQ and β-adrenoceptor agonists as a dilator of mouse small airways. Further investigation of the mechanisms underlying the relatively greater efficacy of RGZ under these conditions are warranted and should be extended to include studies in human asthmatic airways.
Bourke JE, Bai Y, Donovan C, Esposito JG, Tan X, Sanderson MJ: Novel small airway bronchodilator responses to rosiglitazone in mouse lung slices. Am J Respir Cell Mol Biol. 2013, [Epub ahead of print]
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- Rosiglitazone is a superior bronchodilator compared to chloroquine and β-adrenoceptor agonists in mouse lung slices
Jean Ni Cheong
Jane Elizabeth Bourke
- BioMed Central
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