Expression of P2X₃ and P2X₅ Myenteric Receptors Varies During the Intestinal Postnatal Development in the Guinea Pig

Abstract

P2X₃ receptor expression in various tissues appears to be modulated by age. In the present study, we used single cell RT-PCR to determine the number of P2X₃ positive myenteric neurons at different stages of guinea pig postnatal development, and we tested if similar changes also occur to other myenteric P2X receptors. Moreover, we carried out whole-cell recordings using Patch Clamp techniques to determine possible changes in P2X receptors sensitivity to ATP and α,β-methylene ATP (α,β-meATP) between newborn and adult animals. Our data indicate that P2X₃ subunit transcripts are present in a larger number of myenteric neurons from newborn guinea pigs whereas P2X₅ mRNA is found more frequently in adults. Expression of P2X₂ and P2X₄ transcripts does not change during postnatal development. In newborn animals, virtually all neurons expressing P2X₃ also expressed P2X₂ transcripts. This is important because these two subunits are known to form heteromeric channels. ATP potency to activate P2X receptors in neurons of both newborn and adult animals was the same. α,β-meATP, a known P2X₃ receptor agonist, induces only a marginal current despite the fact of the higher presence of P2X₃ subunits in newborns. These findings imply that P2X₃ subunits are mainly forming heteromeric, α,β-meATP insensitive channels perhaps because P2X₃ contributes with only one subunit to the heterotrimers while the other subunits could be P2X₂, P2X₄, or P2X₅.