The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system

Adenosine 5'-triphosphate (ATP) excites 70-90% of enteric neurons through P2X type purine receptors, and is likely to be an enteric neurotransmitter. Recent studies indicate that the P2X(2) subunit is expressed by specific subgroups of enteric neurons, and that there are enteric neurons that are responsive to ATP but lack this subunit. In the present work, we have investigated whether the P2X(3) subunit is similarly localised to specific subgroups of neurons, and whether these are different from the P2X(2) subunit-expressing neurons. The P2X(3) subunit was localised by immunohistochemistry to nerve cells of the myenteric ganglia of the stomach, small and large intestines, and nerve cells of the submucosal ganglia in the small and large intestines of the guinea pig. All immunoreactivity was absorbed with the P2X(3) receptor peptide against which the antiserum was raised. In myenteric ganglia of the ileum, P2X(3) receptor immunoreactivity was in calretinin, enkephalin and nitric oxide synthase (NOS)-immunoreactive neurons. In submucosal ganglia, all calretinin-immunoreactive nerve cells were P2X(3) receptor immunoreactive. In the submucosal ganglia of the ileum, 13 +/- 3% of neuropeptide Y (NPY)-immunoreactive neurons were also P2X(3) receptor immunoreactive, whereas in the distal colon, almost all NPY-expressing nerve cells were P2X(3) receptor immunoreactive. The localisation of the P2X(3) subunit was largely distinct from that of the P2X(2) subunit, although both subunits occur in some NOS neurons, where P2X(2) and P2X(3) subunits may form heteromeric receptors. Unlike the P2X(2) subunit, the P2X(3) subunit is not expressed in intrinsic sensory neurons in the ileum. It is concluded that the P2X(3) receptor subunit is expressed in specific functional groups of neurons-, the major types are excitatory and inhibitory muscle motor neurons, ascending interneurons and cholinergic secretomotor neurons. (C) 2002 Elsevier Science B.V All rights reserved.