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

Abstract

Diadenosine polyphosphates (Ap(n)As, n=3 - 7) and adenosine polyphospho guanosines (Ap(n)Gs, n=3 - 6) are naturally occurring vasoconstrictor substances found in platelets. These vasoconstrictor actions are thought to be mediated through the activation of P2X receptors for 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 dissociated artery smooth muscle cells. P2X(1) receptor immunoreactivity was detected in the smooth muscle layer of artery rings. The sensitivity to alpha,beta-methylene ATP and desensitizing nature of rat mesenteric artery P2X receptors correspond closely to those of recombinant P2X(1) receptors. Ap(4)A, Ap(5)A and Ap(6)A evoked concentration dependent P2X receptor inward currents which desensitized during the application of higher concentrations of agonist. The agonist order of potency was Ap(5)A> or = Ap(6)A> or = Ap(4)A >> Ap(3)A. Ap(2)A and Ap(7)A were ineffective. Similar results were obtained in contraction studies except for Ap(7)A which evoked a substantial contraction. Ap(n)Gs (n=2 - 6)(30 microM) evoked P2X receptor inward currents in mesenteric artery smooth muscle cells. Ap(n)Gs (n=4 - 6) were less effective than the corresponding Ap(n)A. This study shows that at physiologically relevant concentrations Ap(n)As and Ap(n)Gs can mediate contraction of rat mesenteric arteries through the activation of P2X(1)-like receptors. However the activity of the longer chain polyphosphates (n=6 - 7) may be overestimated in whole tissue studies due to metabolic breakdown to yield the P2X receptor agonists ATP and adenosine tetraphosphate. British Journal of Pharmacology (2000) 129, 124 - 130