By Corcos, Jacques; Ginsberg, David; Karsenty, Gilles

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57 Muscarinic receptors have also been located on the urothelium/suburothelium,25,28,58 but their functional importance has not been clarified. 61 demonstrated an inhibitory effect of systemically given oxybutynin on the afferent part of the ­micturition reflex in rats by recording afferent activity in the pelvic nerve. 22,64 Adrenergic mechanisms Adrenergic nerves Fluorescence histochemical studies have shown that the body of the detrusor receives a relatively sparse innervation by noradrenergic nerves.

Parts of the beneficial effects of α1-AR antagonists in the amelioration of storage symptoms in the LUT could be derived from their inhibitory effect on neurogenic inflammatory responses. All α1-AR subtypes can be located in the urothelium, and it has been suggested, based on rat studies,74 that α1AARs can modulate bladder afferent activity under pathophysiological conditions. 69,90,91 The generally accepted mechanism by which β-ARs induce detrusor relaxation in most of the species is activation of adenylyl cyclase with the subsequent formation of cAMP.

CGMP, in turn, regulates protein phosphorylation, ion channel conductivity, and phosphodiesterase (PDE) activity. 208–212 Since cAMP seems to be more important than cGMP for detrusor function, the cAMP pathway in this tissue has been the most extensively investigated pathway. 213–217 demonstrated the presence of five PDE isoenzymes (PDE1–5) in human and porcine detrusor and suggested that the cAMP pathway and the calcium/calmodulinstimulated PDE (PDE1) could be of functional importance in the regulation of detrusor tone.

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