1. Adenosine-5'-triphosphate (ATP) is known to exert a variety of biological effects via the activation of either ionotropic P2x- or G-protein coupled P2Y-purinoceptor subtypes. In this study the effects induced by ATP and ATP analogues on rat bladder strips were characterized at resting tone and in carbachol-prestimulated tissues. 2. ATP exerted a clear concentration-dependent biphasic response, which was maximal at 1 mM concentration and was characterized by an immediate and transient contraction, followed by a slower sustained relaxation. The receptor mediating contraction was susceptible to desensitization by ATP and by the ATP analogue, alpha,beta-methyleneATP (alpha,beta-meATP) showing the typical features of the P2x-purinoceptor; conversely, ATP-evoked relaxation did not undergo tachyphylaxis following either ATP or alpha,beta-meATP. 3. The slower and sustained relaxant phase seemed to be due to activation of P2Y-purinoceptors, based on responses obtained with the P2Y agonist, 2-methyl-thioATP (2-meSATP) and, more importantly, based on the clear involvement of the G-proteins. In fact, the G-protein activator, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) significantly potentiated and the G-protein blocking agent, guanosine 5'-O-(2-thio-diphosphate) (GDP beta S) completely abolished the ATP-induced relaxation. No effects were exerted by these two G-protein modulators on the ATP-induced contraction. 4. The relaxant component of the ATP response of bladder tissue was not significantly influenced by nitro-benzyl-thioinosine (NBTI) or by 8-phenyltheophylline (8-PT), suggesting that the contribution of the ATP metabolite adenosine to this response was negligible.

THE BIPHASIC RESPONSE OF RAT VESICAL SMOOTH-MUSCLE TO ATP / C. BOLEGO, C. PINNA, M. ABBRACCHIO, F. CATTABENI, L. PUGLISI. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 114:8(1995), pp. 1557-1562. [10.1111/j.1476-5381.1995.tb14939.x]

THE BIPHASIC RESPONSE OF RAT VESICAL SMOOTH-MUSCLE TO ATP

C. Bolego
Primo
;
C. Pinna
Secondo
;
M. Abbracchio;F. Cattabeni
Penultimo
;
1995

Abstract

1. Adenosine-5'-triphosphate (ATP) is known to exert a variety of biological effects via the activation of either ionotropic P2x- or G-protein coupled P2Y-purinoceptor subtypes. In this study the effects induced by ATP and ATP analogues on rat bladder strips were characterized at resting tone and in carbachol-prestimulated tissues. 2. ATP exerted a clear concentration-dependent biphasic response, which was maximal at 1 mM concentration and was characterized by an immediate and transient contraction, followed by a slower sustained relaxation. The receptor mediating contraction was susceptible to desensitization by ATP and by the ATP analogue, alpha,beta-methyleneATP (alpha,beta-meATP) showing the typical features of the P2x-purinoceptor; conversely, ATP-evoked relaxation did not undergo tachyphylaxis following either ATP or alpha,beta-meATP. 3. The slower and sustained relaxant phase seemed to be due to activation of P2Y-purinoceptors, based on responses obtained with the P2Y agonist, 2-methyl-thioATP (2-meSATP) and, more importantly, based on the clear involvement of the G-proteins. In fact, the G-protein activator, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) significantly potentiated and the G-protein blocking agent, guanosine 5'-O-(2-thio-diphosphate) (GDP beta S) completely abolished the ATP-induced relaxation. No effects were exerted by these two G-protein modulators on the ATP-induced contraction. 4. The relaxant component of the ATP response of bladder tissue was not significantly influenced by nitro-benzyl-thioinosine (NBTI) or by 8-phenyltheophylline (8-PT), suggesting that the contribution of the ATP metabolite adenosine to this response was negligible.
rat bladder, ATP
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/187166
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