Purinergic signalling in the urinary tract in health and disease

Abstract

Purinergic signalling is involved in a number of physiological and pathophysiological activities in the lower urinary tract. In the bladder of laboratory animals there is parasympathetic excitatory cotransmission with the purinergic and cholinergic components being approximately equal, acting via P2X1 and muscarinic receptors, respectively. Purinergic mechanosensory transduction occurs where ATP, released from urothelial cells during distension of bladder and ureter, acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex, via low threshold fibres, and nociception, via high threshold fibres. In human bladder t h e p u r i n e rg i c c o m p o n e n t o f p a r a s y m p a t h e t i c cotransmission is less than 3 %, but in pathological conditions, such as interstitial cystitis, obstructed and neuropathic bladder, the purinergic component is increased to 40 %. Other pathological conditions of the bladder have been shown to involve purinoceptor-mediated activities, including multiple sclerosis, ischaemia, diabetes, cancer and bacterial infections. In the ureter, P2X7 receptors have been implicated in inflammation and fibrosis. Purinergic therapeutic strategies are being explored that hopefully will be developed and bring benefit and relief to many patients with urinary tract disorders.

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

“…1]. This assertion has been confirmed in many diseases, such as IBS and interstitial cystitis [6]. Clinical and fundamental research had found that a variety of analgesic drugs have good efficacy during the treatment of visceral pain, thus showing a broad therapeutic potential [7,8].…”

Three Gaseous Neurotransmitters, Nitric oxide, Carbon Monoxide, and Hydrogen Sulfide, Are Involved in the Neurogenic Relaxation Responses of the Porcine Internal Anal Sphincter

“…4 In other tissues such as the bladder, ATP is able to induce smooth muscle relaxation via 3 possible mechanisms: (1) directly via P2Y receptors, (2) indirectly by inducing NO release from epithelial cells, and (3) indirectly via P1 receptors after being broken down to adenosine. 13 However, in the current studies the mucosa had been removed before tissues were set up and neither the P2-receptor antagonist suramin, nor the P1-receptor antagonist 8-phenyltheophyline had any effect on relaxations, thus ruling out a role for ATP in relaxation responses of this tissue.…”

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

“…In pathological conditions, including interstitial cystitis and obstructed and neurogenic bladder, the purinergic component of parasympathetic cotransmission is greatly increased 29 . Bladder inflammation induced by CYP in rats sensitizes and increases P2X3 receptor function 30 .…”