Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin

The distribution of P2Y(2) receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y(2) with P2X(2) and P2X(3) receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining methods. The results showed that P2Y(2)-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum, ileum and colon. The typical morphology of P2Y(2)-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y(2)-ir neurons could be Dogiel type 1. About 40-60% P2X(3)-ir neurons were immunoreactive for P2Y(2) in the myenteric plexus and all the P2X(3)-ir neurons expressed the P2Y(2) receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive for P2Y(2), especially in the myenteric plexus of the small intestine; no P2Y(2)-ir neurons were immunoreactive for P2X(2) receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated depolarizations could be those neurons expressing both P2Y(2)-ir and P2X(3)-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut.