Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle

Abstract

The airways and the urinary bladder are both hollow organs serving very different functions, i.e. air flow and urine storage, respectively. While the autonomic nervous system seems to play only a minor if any role in the physiological regulation of airway tone during normal breathing, it is important in the physiological regulation of bladder smooth muscle contraction and relaxation. While both tissues share a greater expression of M 2 than of M 3 muscarinic receptors, smooth muscle contraction in both is largely mediated by the smaller M 3 population apparently involving phospholipase C activation to only a minor if any extent. While smooth muscle in both tissues can be relaxed by β-adrenoceptor stimulation, this primarily involves β 2 -adrenoceptors in human airways and β 3 -adrenoceptors in human bladder. Despite activation of adenylyl cyclase by either subtype, cyclic adenosine monophosphate plays only a minor role in bladder relaxation by β-agonists; an important but not exclusive function is known in airway relaxation. While airway β 2 -adrenoceptors are sensitive to agonist-induced desensitization, β 3 -adrenoceptors are generally considered to exhibit much less if any sensitivity to desensitization. Gene polymorphisms exist in the genes of both β 2 -and β 3 -adrenoceptors. Despite being not fully conclusive, the available data suggest some role of β 2 -adrenoceptor polymorphisms in airway function and its treatment by receptor agonists, whereas the available data on β 3 -adrenoceptor polymorphisms and bladder function are too limited to allow robust interpretation. We conclude that the distinct functions of airways and urinary bladder are reflected in a differential regulation by the autonomic nervous system. Studying these differences may be informative for a better understanding of each tissue.

Effect of pre-contraction on β-adrenoceptor-mediated relaxation of rat urinary bladder

“…This “resistance” of carbachol-induced tone against relaxation did not apply to the receptor-independent relaxation by forskolin. As the autonomic regulation of smooth muscle tone in the bladder and airways has many similarities [ 17 ], it is interesting to note that studies on human airways has also reported that β-adrenoceptor agonists cause weaker relaxation against contraction induced by carbachol than against other stimuli [ 18 , 19 ], thus indirectly supporting our findings. One possible mechanistic explanation of these findings is a specific interaction between M 2 muscarinic and β-adrenergic receptors as has been proposed in rats [ 20 ] and mice [ 21 ].…”

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

“…The EFS was performed at a frequency that elicited similar maximal force and RLC phosphorylation responses. Although trachea and other smooth muscles express M2 and M3 receptors, smooth muscle contraction of the airways occurs largely, if not exclusively, via M3 receptors (Michel & Parra, ). Thus, differences in the chemical effector or muscarinic receptors do not provide a satisfactory explanation.…”

How reliable are G-protein-coupled receptor antibodies?

“…However, the problem apparently goes well beyond the homology of closely related GPCR subtypes. For example, airways express only the M 2 and M 3 subtype of muscarinic receptors (Michel and Parra 2008) but double-knock-out mice lacking both subtypes still stained positive for M 2 and M 3 receptor antibodies (Jositsch et al 2009). Similarly, triple knock-out mice lacking all three α 1 -adrenoceptor subtypes show similar staining patters as wild-type mice (Jensen et al 2009).…”