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Novel Excitatory Effects of Adenosine Triphosphate on Contractile and Pacemaker Activity in Rabbit Urethral Smooth Muscle

Bradley, Eamonn and Kadima, Sonia and Drumm, Bernard and Hollywood, Mark A. and Thornbury, Keith D. and McHale, Noel G. and Sergeant, Gerard P. (2010) Novel Excitatory Effects of Adenosine Triphosphate on Contractile and Pacemaker Activity in Rabbit Urethral Smooth Muscle. The Journal of Urology, 183. pp. 801-811. ISSN 0022-5347/10/1832-0801/0

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Abstract

Purpose: Adenosine triphosphate is thought to be an important neurotransmitter in urethral smooth muscle but its physiological role is still unclear. We characterized the effects of adenosine triphosphate on contractile and pacemaker activity in rabbit urethral smooth muscle. Materials and Methods: Tension recordings were made from strips of rabbit proximal urethral smooth muscle. Membrane currents from freshly isolated smooth muscle cells and interstitial cells of Cajal were recorded using the patch clamp technique. Intracellular Ca 2� was measured using confocal microscopy. Results: Exogenous application of adenosine triphosphate (10 �M) evoked robust contractions that were inhibited by the type 2 purinergic receptor blocker suramin (100 �M) and the selective type 2 purinergic Y1 receptor antagonist MRS2500 (Tocris Bioscience, Ellisville, Missouri) (100 nM). Application of the type 2 purinergic Y receptor agonist 2-MeSADP (1 �M) mimicked the effects of adenosine triphosphate. When smooth muscle cells were studied under voltage clamp at �60 mV, adenosine triphosphate evoked a large single inward current (greater than 1.2 nA) but 2-MeSADP produced a small current (about 16 pA). In contrast, when interstitial cells of Cajal were held at �60 mV, they showed spontaneous transient inward currents that were increased in frequency by adenosine triphosphate and 2-MeSADP. These excitatory effects were inhibited by suramin and MRS2500. Interstitial cells of Cajal showed spontaneous Ca 2� waves that were increased in frequency by adenosine triphosphate and 2-MeSADP. These effects were also inhibited by suramin and MRS2500. Conclusions: Contractile effects of adenosine triphosphate in urethral smooth muscle are mediated by the activation of type 2 purinergic Y receptors on interstitial cells of Cajal.

Item Type: Article
Uncontrolled Keywords: Urethra; Muscle, smooth; Urinary incontinence; Muscle contraction; Adenosine triphosphate
Subjects: Science
Research Centres: Smooth Muscle Research Centre
Depositing User: Concepta Woods
Date Deposited: 19 Nov 2011 15:27
Last Modified: 11 Nov 2014 16:10
URI: http://eprints.dkit.ie/id/eprint/64

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