Effects of diadenosine polyphosphates (Ap(n)As) and adenosine polyphospho guanosines (Ap(n)Gs) on rat mesenteric artery P2X receptor ion channels

1 Diadenosine polyphosphates (Ap(n)As, n = 3-7) and adenosine polyphospho g uanosines (Ap(n)Gs, n = 3-6) are naturally occurring vasoconstrictor substa nces found in platelets, These vasoconstrictor actions are thought to be me diated through the activation of P2X receptors far ATP. The effects of Ap(n )As and Ap(n)Gs at P2X receptors on rat mesenteric arteries were determined in contraction studies and using the patch clamp technique on acutely diss ociated artery smooth muscle cells. 2 P2X(1) receptor immunoreactivity was detected in the smooth muscle layer of artery rings. The sensitivity to alpha,beta-methylene ATP and desensitiz ing nature of rat mesenteric artery P2X receptors correspond closely to tho se of recombinant P2X(1) receptors. 3 Ap(4)A, Ap(5)A and Ap(6)A evoked concentration dependent P2X receptor inw ard currents which desensitized during the application of higher concentrat ions of agonist. The agonist order of potency was Ap(5)A greater than or eq ual to Ap(6)A greater than or equal to Ap(4)A > > Ap(3)A. Ap(2)A and Ap(7)A were ineffective. Similar results were obtained in contraction studies exc ept for Ap(7)A which evoked a substantial contraction. 4 Ap(n)Gs (n = 2-6)(30 mu M) evoked P2X receptor inward currents in mesente ric artery smooth muscle cells. Ap(n)Gs (n = 4-6) were less effective than the corresponding Ap(n)A. 5 This study shows that at physiologically relevant concentrations Ap(n)As and Ap(n)Gs call mediate contraction of rat mesenteric arteries through the activation of PZX(1)-like receptors. However the activity of the longer ch ain polyphosphates (n = 6-7) may be overestimated In whole tissue studies d ue to metabolic breakdown to yield the P2X receptor agonists ATP and adenos ine tetraphosphate.