Abstract
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. alpha,ss-methylene ATP (alpha,beta-meATP) evoked transient concentration-dependent contractions in mesenteric arteries with EC(50) values of 0.4, 2.5 and 107 microM for small, medium and large arteries respectively. Suramin (10 - 100 microM) produced substantial parallel rightward shifts of the concentration-response curve to alpha,beta-meATP in small and medium-sized arteries with pA(2) of 5.1. Responses in large vessels were unaffected by suramin. Immunohistochemical analysis of arterial sections revealed no substantial differences in expression patterns of P2X receptors between different sizes of artery. P2X(1) receptors were expressed at high levels, P2X(4) and P2X(5) receptors were also detected on smooth muscle. The P2X receptor response is dominated by P2X(1) receptor in small and medium arteries but the nature of the receptor mediating the suramin insensitive alpha,beta-meATP mediated response in large arteries is unclear. The P2Y receptor agonist UTP was significantly more potent in small than in medium or large arteries (EC(50) values: 15.0 microM small, 88.5 microM 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 microM). The sensitivity to UTP and suramin indicates the presence of P2Y(2) receptors. 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.