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Eur J Pharmacol. 2008 Oct 24;595(1-3):84-9. doi: 10.1016/j.ejphar.2008.07.057. Epub 2008 Aug 5.

Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two calcium signal pathways in the longitudinal muscle of mouse distal colon.

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1
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, UniversitĂ  di Palermo, Viale delle Scienze, Palermo, Italy.

Abstract

Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or the calcium channel blocker, nifedipine, failed to modify the contractile responses to ATP or ADPbetaS, which were virtually abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. Neomycin or U-73122, phospholipase C inhibitors, or 2-aminoethoxy-diphenylborate (2-APB), membrane-permeant IP(3) receptor inhibitor reduced the response to ATP, whilst ryanodine or ruthenium red, inhibiting calcium release from ryanodine-sensitive stores, abolished the response to ADPbetaS. Responses to maximally effective concentrations of ATP and ADPbetaS were not fully additive. Desensitisation with ADPbetaS antagonized the contractile effects of ATP, as desensitisation with ATP antagonized the response to ADPbetaS. In the longitudinal muscle of mouse distal colon, ATP and ADPbetaS induce muscular contraction via a P2Y receptor, coupled to differential signal pathways leading to intracellular calcium increase.

PMID:
18713670
DOI:
10.1016/j.ejphar.2008.07.057
[Indexed for MEDLINE]
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