Properties of P2X and P2Y receptors are dependent on artery diameter in the rat mesenteric bed

Abstract

1. P2 receptor mediated contractile responses have been characterized in different diameter arteries from the rat mesenteric arterial vasculature (first, second to third and fifth to sixth order for large, medium and small arteries) using wire myograph and diamtrak video imaging. 2. α,β-methylene ATP (α,β-meATP) evoked transient concentration-dependent contractions in mesenteric arteries with EC50 values of 0.4, 2.5 and 107 μM for small, medium and large arteries respectively. 3. Suramin (10-100 μM) produced substantial parallel rightward shifts of the concentration-response curve to α,β-meATP in small and medium-sized arteries with pA2 of 5.1. Responses in large vessels were unaffected by suramin. 4. Immunohistochemical analysis of arterial sections revealed no substantial differences in expression patterns of P2X receptors between different sizes of artery. P2X1 receptors were expressed at high levels, P2X4 and P2X5 receptors were also detected on smooth muscle. The P2X receptor response is dominated by P2X1 receptor in small and medium arteries but the nature of the receptor mediating the suramin insensitive α,β-meATP mediated response in large arteries is unclear. 5. The P2Y receptor agonist UTP was significantly more potent in small than in medium or large arteries (EC50 values: 15.0 μM small, 88.5 μM diamtrak medium 1.6 mM myography medium and 1.4 mM large). Responses in both small and medium-sized vessels were reduced by suramin (30-100 μM). The sensitivity to UTP and suramin indicates the presence of P2Y2 receptors. 6. This study shows that P2 receptors do not have a homogenous phenotype throughout the mesenteric vascular bed and that the properties depend on artery size.