Purinergic neurotransmission has been regarded as major component of non-adrenergic, noncholinergic (NANC) contraction in detrusor smooth muscle. Although in normal human detrusor, this contraction seems to be small, the importance of the NANC component for detrusor contraction in disease conditions such as detrusor overactivity remains to be established. Based on many evidences for purinergic contributions in lower urinary tract, ATP and purinoceptors has been suggested to be involved in both efferent and afferent mechanism in voiding reflex. ATP signaling via P2X1 receptors plays an important role in efferent neural control of urinary bladder function, although to varying degrees across species from experimental animals to men. The efferent function of purinoceptors may be enhanced in detrusor overactivity and aging. ATP also suggested being involved in mechanosensory transmission, via activation of P2X3 and P2X2/3 receptors on sensory afferent nerves. The afferent function of purinoceptors may be related with pathophysiology of overactive bladder or interstitial cystitis, mediating bladder hyperexicitability. These results suggest that the selective antagonists for the purinoceptors may offer better relief of sensory and motor symptoms for overactive bladder or interstitial cystitis patients in the future.
Adenosine Triphosphate ; Aging ; Animals ; Cystitis, Interstitial ; Humans ; Male ; Muscle, Smooth ; Negotiating ; Receptors, Purinergic P2X1 ; Receptors, Purinergic* ; Reflex* ; Synaptic Transmission ; Urinary Bladder ; Urinary Bladder, Overactive ; Urinary Tract

To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.
Aging ; physiology ; Animals ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression Regulation ; Kidney Diseases ; drug therapy ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; genetics ; Receptors, Purinergic P2X3 ; genetics ; Urinary Bladder ; metabolism

We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.
Action Potentials ; physiology ; Adenosine Triphosphate ; metabolism ; Animals ; Dental Pulp ; innervation ; physiology ; Nociceptors ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; metabolism ; Receptors, Purinergic P2X3 ; metabolism ; Tissue Distribution ; Trigeminal Nerve ; cytology ; metabolism