PHARMACOLOGICAL EVIDENCE FOR A RECEPTOR MEDIATING SUSTAINED NUCLEOTIDE-EVOKED CONTRACTIONS OF RAT AORTA IN THE PRESENCE OF UTP

The contractile effect of ATP given alone or in the presence of other nucleotides was studied in rat aortic strips. A sustained contraction in response to ATP (30 mu M to 10 mM) was observed during UTP exposure instead of the fast transient contraction produced via P-2X purinocep tor activation in the absence of UTP, and contrary to the relaxation e licited when the tone had been raised by noradrenaline and KCl. This s ustained ATP effect was produced in the smooth muscle and not via the same mechanism through which UTP elicited contraction, since the contr actions in response to UTP and ATP were additive. They were also coupl ed to different transduction pathways: the effect of UTP but not that of ATP was pertussis toxin-sensitive. In contrast to the fast transien t ATP contraction during basal tone, the sustained response was not de sensitized by alpha,beta-methylene ATP exposure (30 mu M), but was inh ibited by reactive blue 2 (10 and 30 mu M) Among the nucleotides assay ed, UDP and ATP gamma S also enabled ATP to elicit a sustained contrac tion. ADP, AMP, dATP, 2-methylthio ATP, alpha,beta-methylene ATP, GTP, GDP, GMP, CTP and ITP also induced a sustained contraction in the pre sence of UTP. However, adenosine (1 mM) and adenine (0.3 to 3 mM) indu ced relaxation when the tone had been raised by UTP. According to thes e results a non-selective nucleotide receptor, different from the P, p urinoceptors functionally characterized so far, seems to mediate susta ined contractions in rat aortic strips in the presence of UTP, UDP or ATP gamma S. (C) 1998 Elsevier Science B.V. All rights reserved.