Overactive bladder--pharmacological aspects.
The micturition reflex can be initiated by contraction or distension of detrusor smooth muscle cells, or by signals from the urothelium. It has been shown that bladder distension causes release of ATP from the urothelium, and that ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably the activation of afferent fibres during bladder filling involves not only ATP, but a cascade of inhibitory and stimulatory transmitters/mediators. These mechanisms may be targets for future drugs. Both in the normal and functionally disturbed bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, interstitial cystitis, and also in the ageing bladder, a non-cholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions. Drags blocking different P2X receptor subtypes, or counteracting bladder contraction via other mechanisms, e.g. beta3-adrenoceptor stimulation, may be developed for treatment of the overactive bladder.
Andersson
K E
KE
Department of Clinical Pharmacology, Lund University Hospital, Sweden. Karl-Erik.Andersson@klinfarm.lu.se
D000255:Adenosine Triphosphate / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D012018:Reflex / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy*; D014554:Urination / Q000502:physiology*
D011453:Prostaglandins; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002211:Capsaicin