A(1) Adenosine Receptor-Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder

作者：Searl Timothy J^*; Dynda Danuta I; Alanee Shaheen R; El Zawahry Ahmed M; McVary Kevin T; Silinsky Eugene M

来源：Journal of Pharmacology and Experimental Therapeutics, 2016, 356(1): 116-122.

DOI：10.1124/jpet.115.228882

The potential role of A(1) adenosine receptors in modulating neuromuscular transmission in the detrusor muscle of the urinary bladder has been tested in human and murine preparations with the intent to determine the viability of using adenosine receptor agonists as adjuncts to treat overactive bladder. In human detrusor muscle preparations, contractile responses to electrical field stimulation were inhibited by the selective A(1) adenosine receptor agonists 2-chloro-N-6-cyclopentyladenosine, N-6-cyclopentyladenosine (CPA), and adenosine (rank order of potency: 2-chloro-N-6-cyclopentyladenosine. CPA. adenosine). Pre-treatment with 8-cyclopentyl-3-[3-[[4(fluorosulphonyl) benzoyl] oxy] propyl]-1-propylxanthine, an irreversible A(1) antagonist, blocked the effects of CPA, thus confirming the role of A(1) receptors in human detrusor preparations. In murine detrusor muscle preparations, contractions evoked by electrical field stimulation were reduced by CPA or adenosine. Amplitudes of the P2X purinoceptor-mediated excitatory junctional potentials (EJPs) recorded with intracellular microelectrodes were reduced in amplitude by CPA and adenosine with no effect on the spontaneous EJP amplitudes, confirming the prejunctional action of these agents. 8-Cyclopentyltheophylline, a selective A(1) receptor antagonist, reversed the effects ofCPA on EJP amplitudes with no effect of spontaneous EJPs, confirming the role of A(1) receptors in mediating these effects.

• 出版日期2016-1
• 单位西北大学