Autonomic nervous dysfunction is a common complication of diabetes mellitus. Previously, we have hypothesized that alterations in sensitivity/responsiveness to noradrenaline (NA), ATP and Neuropeptide Y (NPY) may underlie functional abnormalities of diabetic blood vessels (Speirs et al., 2006). In this study, changes in expression of predominant adrenergic (α_1a-adrenoceptor: α_1a-AR) and purinergic (P2X₁) receptors were investigated in tail arteries of streptozotocin-treated rats and Akita mice (both type 1 diabetes models); expressional studies were supplemented with functional studies in rat tail arteries. Tail arteries were excised from diabetic (60 mg.kg-1 streptozotocin, i.p. injection at 8 weeks) and control Sprague-Dawley rats at 20 weeks and Akita mice and controls at 10 weeks. Receptor expression was determined at mRNA and protein level using RT-PCR and Western blotting (normalized to β-actin mRNA and β-actin respectively). Isometric contractions were recorded from proximal sections of rat tail arteries (3-5 mm length, endothelium-denuded). Agonist concentration response curves were expressed as a % of contraction induced by 60 mM KCl. Maximal contraction induced by NA was greater in arteries of diabetics (279±17%, mean ± S.E., n=20, P<0.001; 2-way ANOVA, Bonferroni post-hoc tests) relative to arteries of age-matched control rats (n=20, 179±12%). α_1a-AR expression was not increased in arteries of diabetic rats relative to controls at mRNA (1.16±0.16 vs. 1.01±0.05; n=5 each, unpaired students t-test) or protein level (1.17±0.31 vs. 0.79-±0.15; n=5 each). Maximal contraction produced β,γ-methylene ATP was greater in arteries of diabetics (P<0.001; 103±9%; n=20) relative to age-matched control rats (69.9±11%; n=20). Parallel increases in P2X₁ receptor expression were observed at both mRNA (P<0.01; 4.09 + 0.67; n=5) and protein level (P<0.01; 0.48±0.04) relative to age-matched controls (1.22±0.37; 0.24±0.01; n=5). Similarly, P2X₁ receptor mRNA expression was increased in tail arteries of diabetic mice compared to age-matched control mice (P<0.05; 0.93±0.15 vs. 0.49±0.18; n=5 each) however in contrast to the absence of expressional changes in tail arteries of diabetic rats, α_1a-adrenoceptor mRNA expression was also increased (P<0.05; 1.54±0.26; n=5) in tail arteries of diabetic mice relative to age-matched control mice (0.94±0.06; n=5). These data indicate that augmented expression of P2X₁ receptors, but not of α_1a-AR, may contribute to changes in peripheral vessel function in Type 1 diabetes; contractile studies in Akita diabetic mice are awaited to confirm the contribution of the observed augmented expression of P2X₁ receptors and α_1a-AR to altered function in diabetes.