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Role of ATP and related purines in inhibitory neurotransmission to the pig urinary bladder neck.

Hernández, Medardo, Knight, Gillian E., Wildman, Scott S.P., Burnstock, Geoffrey (2009) Role of ATP and related purines in inhibitory neurotransmission to the pig urinary bladder neck. British journal of pharmacology, 157 (8). pp. 1463-1473. ISSN 0007-1188. E-ISSN 1476-5381. (doi:10.1111/j.1476-5381.2009.00314.x) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

BACKGROUND AND PURPOSE As adenosine 5'-triphosphate (ATP) is one of the inhibitory mediators of the bladder outflow region, this study investigates the possible release of ATP or related purines in response to electrical field stimulation (EFS) and the purinoceptor(s) involved in nerve-mediated relaxations of the pig urinary bladder neck. EXPERIMENTAL APPROACH Urothelium-denuded and intact phenylephrine-precontracted strips were mounted in organ baths containing physiological saline solution at 37 degrees C and gassed with 95% O(2) and 5% CO2 for isometric force recordings. KEY RESULTS EFS, in the presence of atropine, guanethidine and N(G)-nitro-L-arginine, and exogenous purines, produced frequency- and concentration-dependent relaxations respectively. Adenosine 5'-diphosphate (ADP) and adenosine were more potent than ATP in producing relaxation, while uridine 5'-triphosphate, uridine 5'-diphosphate and alpha,beta-methylene ATP were less effective. The non-selective P2 antagonist suramin, and the P2Y(1) and P1 receptor blockers 2'-deoxy-N6-methyladenosine 3',5'-bisphosphate tetrasodium and 8-(p-sulphophenyl)theophylline, respectively, inhibited the responses to EFS and ATP. The P1 agonist's potency was: 5'-N-ethylcarboxamidoadenosine (NECA)>4-2[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene propanoic acid hydrochloride>2-chloro-N(6)-cyclopentyladenosine>-2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide = adenosine. 4-(-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol, an A(2A) antagonist, reduced the relaxations to EFS, adenosine and NECA. In urothelium-intact samples, relaxations to EFS and purines were smaller than in urothelium-denuded preparations. Neuronal voltage-gated Na(+) channels blockade failed to modify ATP relaxations. At basal tension, EFS- and ATP-induced contractions were resistant to desensitization or blockade of P2X(1) and P2X(3) receptors. CONCLUSIONS AND IMPLICATIONS ATP is involved in the non-adrenergic, non-cholinergic, non-nitrergic inhibitory neurotransmission in the pig bladder neck, producing relaxation largely through muscle A(2A) receptors after breakdown to adenosine, and P2Y(1) receptors after breakdown to ADP. Antagonists of these receptors may be useful for urinary incontinence treatment produced by intrinsic sphincteric deficiency.

Item Type: Article
DOI/Identification number: 10.1111/j.1476-5381.2009.00314.x
Additional information: APC checked 10.3.16
Uncontrolled keywords: EFS; NANC inhibitory neurotransmission; ATP; ADP; adenosine; P2Y(1) - and A(2A) -receptors; pig urinary bladder neck
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 10 Dec 2015 15:03 UTC
Last Modified: 29 May 2019 16:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53058 (The current URI for this page, for reference purposes)
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