Article

Pharmacological and molecular characterization of P2X receptors in rat pelvic ganglion neurons

British Journal of Pharmacology (Impact Factor: 5.07). 09/1998; 125(4):771 - 781. DOI: 10.1038/sj.bjp.0702118

ABSTRACT 1The presence and characteristics of P2X receptors on neurons of the rat major pelvic ganglia (MPG) have been studied using whole cell voltage-clamp, in situ hybridization and immunohistochemistry.2Rapid application of ATP (100 μM) to isolated rat MPG neurons induced moderately large inward currents (0.33–5.3 nA) in 39% of cells (108/277). The response to ATP occurred very rapidly, with an increase in membrane conductance, and desensitized slowly.3The concentration-response curve for ATP yielded an EC50 of 58.9 μM. The agonist profile was ATP2MeSATP=ATPS>BzATP, while ,β-MeATP, β,-MeATP, UTP and ADP were all inactive at concentrations up to 100 μM.4The response to ATP was antagonized by suramin (pA2=5.6), reactive blue-2 (IC50=0.7 μM) and pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS).5Lowering the pH from 7.4 to 6.8 produced a marked potentiation (to 339% of control) of the responses to ATP (30 μM), while raising the pH to 8.0 attenuated the responses (to 20% of control). The EC50s for ATP were 28.8, 58.9 and 264 μM at pH 6.8, 7.4 and 8.0, respectively.6Co-application of ATP with Zn2+ produced a marked enhancement of the responses to ATP, with an EC50 of 9.55 μM. In the presence of Zn2+ (30 μM), the EC50 for ATP was decreased to 4.57 μM.7In situ hybridization revealed that the P2X receptor transcripts levels in rat MPG neurons are P2X2>P2X4>P2X1, P2X3, P2X5 and P2X6. The immunohistochemical staining revealed a small number of neurons with strong P2X2 immunoreactivity.8In conclusion, our results indicate that there are P2X receptors present on MPG neurons. The pharmacological characteristics of these receptors, the in situ hybridization and immunohistochemical evidence are consistent with them being of the P2X2 subtype, or heteromultimers, with P2X2 being the dominant component.British Journal of Pharmacology (1998) 125, 771–781; doi:10.1038/sj.bjp.0702118

0 Bookmarks
 · 
55 Views
  • [Show abstract] [Hide abstract]
    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 the purinergic component of parasympathetic 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.
    Purinergic Signalling 11/2013; · 2.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Thiazole is a well-known five-membered heterocyclic compound. Various methods have been worked out for its synthesis. In the last few decades, a lot of work has been done on thiazole ring in order to find new compounds related to this scaffold acting as an antioxidant, analgesic, anti-inflammatory, antimicrobial, antifungal, antiviral, diuretic, anticonvulsant, neuroprotective and antitumor or cytotoxic drugs with lesser side effects. This review presents the up to date development of different thiazole derivatives. Areas covered: This review gives an account of the recent therapeutic patent literature (2008 - 2012) describing the applications of thiazole and its derivatives on selected activities. In this review, many of the therapeutic applications of thiazole derivatives reported in international patents have been discussed. In addition to selected biological data, some of pharmaceutical applications are also summarized. Because of the large number of patents registered in this period relative to thiazole derivatives the attention was focused, in this first part of the review, on inhibitors of phosphatidylinositol-3-kinase, inhibitors of protein kinase and derivatives modulating enzymes related to metabolism. Expert opinion: This review of patented products presents the thiazole ring as the nucleus of the derivatives considered from a medicinal chemistry perspective. The applications are based firstly on the specific enzyme target with very low development in the disease treatment. Most of the described compounds are shown to have beneficial therapeutic effects but at the same time these compounds, selective for 'multi-signaling pathway' targets, may also increase the side-effect potential.
    Expert Opinion on Therapeutic Patents 11/2013; · 3.53 Impact Factor
  • Source

Full-text (2 Sources)

Download
10 Downloads
Available from
May 23, 2014