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TRANSLATIONAL PHYSIOLOGY

Increased relaxation of immature airways to ₂-adrenoceptor agonists is related to attenuated expression of postjunctional smooth muscle muscarinic M₂ receptors

¹Université Victor Segalen Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, and Institut National de la Santé et de La Recherche Médicale E 356, Bordeaux, France; and ²CHU Bordeaux, Hôpital Pédiatrique, Unité de Pneumologie Pédiatrique et Centre de Recherche (CEDRE), Bordeaux, France

Submitted 30 August 2004 ; accepted in final form 24 November 2004

ABSTRACT

Spontaneous or agonist-induced contraction of airway smooth muscle can be observed very early in fetal life, thus explaining the possible occurrence of bronchospasm in very low birth weight infants within the first days of life. In an attempt to better manage such bronchospasms, the aim of the present study was to investigate the age-specific modifications in airway smooth muscle relaxation to ₂-agonists and muscarinic antagonists using a combination of functional and molecular techniques. In the rat, isometric relaxation to the ₂-agonist salbutamol was examined in tracheae; we also examined muscarinic receptor expression (M₂R and M₃R mRNA levels) in airway smooth muscle by immunochemistry, Western blotting, and real-time PCR. Compared with adults, salbutamol-induced relaxation was twofold greater in immature rat isolated tracheae preconstricted by carbachol. This effect was associated with a lower expression of M₂R in the smooth muscle of immature animals (sixfold and almost twofold as assessed by immunochemistry and Western blotting, respectively). Real-time PCR data indicate that changes in M₂R expression according to age occurred at a posttranscriptional level. In adult airways, there was a significantly greater functional efficacy of M₂R blockade by methoctramine compared with that shown in immature rats. Because of the limited availability of human neonate lung tissue, only the molecular part of the study was performed, and we observed a qualitatively similar effect, i.e., a lower M₂R expression in the neonatal airway smooth muscle, although this was quantitatively smaller. We conclude that ₂-agonist-induced relaxation is enhanced in immature compared with adult airways as a result of greater postjunctional M₂R expression in adult airway smooth muscle. This finding may be of importance in the clinical management of bronchoconstriction in neonates.

acetylcholine; albuterol; muscarinic receptor subtypes; physiopathology; trachea

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