Triple label immunohistochemistry was used to study the coexistence
of the catecholamine-synthesising
enzymes dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) and
several neuropeptides
including neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP),
substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin
(SOM) and galanin (GAL) as well as nitric oxide synthase (NOS) in
developing pelvic paraganglion cells in a series of human male fetal,
neonatal and infant specimens ranging
in age from 13 wk of gestation to 3 y postnatal. 13–20 wk old
fetal specimens possessed large clusters of
paraganglion cells lying lateral to the urinary bladder and prostate
gland which were intensely DBH-immunoreactive (-IR) but lacked TH,
NOS and the neuropeptides investigated. With increasing fetal age
small clusters of paraganglion cells were observed in the muscle coat
of the urinary bladder. At 23 wk of
gestation occasional paraganglion cells were NOS or NPY-IR while at
26 wk of gestation the majority of
paraganglion cells were TH-IR and a few were SOM or GAL-IR. Some
postnatal paraganglia within the
bladder musculature contained cells which were all VIP, SP or CGRP-IR
while others displayed coexistence
of NOS and NPY, SP and CGRP, or NPY and VIP. The presence of NOS in certain
paraganglion cells
indicates their capacity to generate nitric oxide (NO). These
results show that human paraganglion cells
develop different phenotypes possibly dependent upon their location
within the bladder wall. A delicate
plexus of branching varicose nerves was observed in the fetal
paraganglia which increased in density with
increasing gestational age. The majority of these nerves were VIP-IR
while others were CGRP, SP, NPY,
NOS or GAL-IR. The presence of nerve terminals adjacent to the
paraganglion cells implies a neural
influence on the functional activity of the paraganglia. Some
paraganglia in the late fetal and early postnatal
specimens contained Timofeew's sensory corpuscles, resembling
pacinian corpuscles in their morphology.
The central nerve fibre of these corpuscles displayed immunoreactivity
for SP, CGRP and NOS, the latter
indicating a possible role for NO in afferent transmission from the
urinary bladder. In addition, a few
corpuscles were penetrated by a noradrenergic nerve fibre
immunoreactive for NPY and TH, which may
have a modulatory role on the sensory receptor.