Aims
of the Study
Adenosine 5’-triphosphate (ATP)
is well recognized as a neurotransmitter in smooth muscle preparations [1,2,3].
There is evidence to show that ATP both causes bladder contractions [1,2,4]
and may have a sensory role in processing physiological information
in the urinary bladder [5]. These effects are likely to be mediated by P2X
receptors [2,4], namely P2X1 and P2X3, respectively.
This study set out to investigate their distribution using subtype-specific
antibodies to localise these receptors in the rat and human urinary bladder.
Methods
Sections of rat and human urinary bladder,
the latter obtained from male donor subjects, were incubated with antibodies
to P2X1 and P2X3 receptors. Antibodies to the sensory
neuropeptide, calcitonin gene-related peptide (CGRP) were used to identify
sensory neurones in the rat [6] and human urinary bladder. Colocalisation studies with the CGRP and P2X3
receptor antibodies were also performed.
Results
P2X1 receptor immunoreactivity was
found on detrusor muscle fibres of both species. P2X3 receptor
immunoreactivity was mainly found in the urothelium and labelling was also
seen in the suburothelial layers of the rat and human urinary bladder. The
sensory innervation of the urinary bladder of both species was shown using
the antibodies to CGRP. No clear evidence for colocalisation of CGRP and
P2X3 immunoreactivity was seen in the urinary bladder of either
species.
Conclusion
This study has confirmed the presence
of P2X1 receptors on the detrusor muscle of the rat [7] and human
urinary bladder. Interestingly, P2X3 receptors were found on
urothelial cells, the first demonstration of a non-neuronal localisation
for P2X3 receptors. No clear evidence was found for the presence
of P2X3 receptors on CGRP-containing nerves and therefore P2X3
receptors may not mediate the sensory response to ATP in the urinary bladder.
References:
1 Burnstock G, Dumsday B, Smythe A.
Atropine resistant excitation of the urinary bladder: the possibility of
transmission via nerves releasing a purine nucleotide. Br J Pharmacol
1972: 44: 451-461
2 Fujii K. Evidence for adenosine triphosphate
as an excitatory transmitter in the guinea-pig, rabbit and pig urinary bladder.
J Physiol 1988: 404: 39-52
3 Burnstock G. Purinergic neurotransmission.
Semin Neurosci 1996: 8: 171-257
4 McMurray G, Dass N, Brading AF. Purinoceptor
subtypes mediating contraction and relaxation of marmoset urinary bladder
smooth muscle. Br J Pharmacol 1998: 123: 1579-1586
5 Ferguson DR, Kennedy I, Burton TJ.
ATP is released from rabbit urinary bladder epithelial cells by hydrostatic
pressure changes - a possible sensory mechanism? J Physiol 1997:
505: 503-511
6 Gabella G, Davis C. Distribution of afferent axons in
the bladder of rats. J Neurocytol 1998: 27: 141-155
7 Vulchanova L, Arvidsson U, Reidl M,
Wang J, Buell G, Suprenant A, North RA, Elde R. Differential distribution
of two ATP-gated ion channels (P2X receptors) determined by immunocytochemistry.
Proc Natl Acad Sci 1996: 93: 8063-8067
