P₂‐purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P_2y‐ but not the P_2x‐purinoceptor

Abstract

I mc-Methylene ATP and ATP both produced concentration-dependent contractions of the isolated mesenteric artery of the rabbit that were not inhibited by reactive blue 2. 2 In preparations where the tone had been raised with noradrenaline, ATP and 2-methylthio ATP, but not a,-methylene ATP, produced relaxations of the vessel. These relaxations were inhibited in the presence of reactive blue 2. 3 Reactive blue 2 did not inhibit the contractions to noradrenaline, and only slightly inhibited relaxations to adenosine and acetylcholine.4 The rank order of potency of purine nucleotide analogues in contracting the vessel was: a,-methylene ATP > P,'y-methylene ATP = 2-methylthio ATP > ATP, and in relaxing the vessel at raised tone was: 2-methylthio ATP > ATP > ,y-methylene ATP > a,-methylene ATP.5 It is concluded from this study that in the isolated mesenteric artery ofthe rabbit, purine nucleotides act via P2y-purinoceptors to cause the muscle to relax and via P2x-purinoceptors to cause the muscle to contract. The results also suggest that reactive blue 2 selectively inhibits responses mediated via the P2y-purinoceptor, at least within a limited concentration range.

P2 purinoceptor regulation of mucin release by airway goblet cells in primary culture

“…The ATP-induced phospholipid release by cultured type II pneumocytes was blocked by reactive blue 2 in a dose-dependent manner (Rice & Singleton, 1989). Reactive blue 2 was previously found to be a specific P2y receptor blocker in smooth muscle preparations (Burnstock & Warland, 1987). In the present HTSE cell culture system, the concentrations of reactive blue 2 which caused phospholipid release in type II pneumocytes did not block the ATP-induced mucin release, but rather increased mucin release by itself (Figure 4).…”

Purinergic and non‐purinergic innervation in the cerebral arteries of the dog

“…These results indicate that there is a regional difference in the ATP response of dog cerebral arteries (Muramatsu et al, 1980). Recently, P2-purinoceptors have been subdivided into P2, and P2y, which are selectively inhibited by x,p-methylene ATP and reactive blue 2, respectively (Burnstock & Kennedy, 1985;Burnstock & Warland, 1987b;Hopwood & Burnstock, 1987). The contraction induced by ATP of the dog basilar artery was abolished by desensitization to x,B-methylene ATP, thereby suggesting that the contractile response, at least, is mediated through the P2h-purinoceptor.…”

“…On the other hand, the relaxant response to ATP was not attenuated by x,-methylene ATP although the pattern of the response was modified. This lack of inhibition may mean that the relaxation induced by exogenous ATP is predominantly mediated through different types of purinoceptors such as P2, or P, (Burnstock & Warland, 1987b). Previously we observed that ATP-induced relaxation of the dog cerebral artery was partially but not completely inhibited by a PI-purinoceptor antagonist, theophylline (Muramatsu et al, 1980).…”

Purinergic receptors in the splanchnic circulation

“…or 95% confidence interval (in parenthesis). EC 50 , EC 40 and EC 20 represent the molar concentration of the agonist nedded to cause 50%, 40% and 20% of the maximum response, respectively; pEC 50 , pEC 40 and pEC 20 are the negative logarithme to base 10 of the EC 50 , EC 40 and EC 20 of an agonist, respectively; pA 2 is the negative logarithme to base 10 of the molar concentration of the antagonist that makes it necessary to double the concentration of the agonist nedded to elicit the original response.…”

“…ATP elicits arterial contraction through stimulation of P2X receptors in the mesenteric artery of the rat [54, 73,85,123,137], guinea-pig [116] and rabbit [20], and in the rat hepatic artery [130] and the guinea-pig portal vein [125]. The P2X 1 subtype is the receptor responsible for the purine nucleotides-induced arterial contractions [54,177].…”