Urinary bladders of normal adult female guinea pigs were analyzed for
anatomical evidence of nerve-mast cell interaction using light microsc
opy and electron microscopy. Nerves, ganglia, and individual nerve fib
ers were visualized on paraffin sections using immunohistochemistry wi
th antisera against the neural antigens neurofilament protein and prot
ein gene product 9.5, and sections were also immunoreacted with antise
ra against the neuropeptides substance P and calcitonin gene-related p
eptide. Separate mast cell populations were identified by counterstain
ing with toluidine blue and alcian blue. Mast cells of both types were
found within nerves and intramural ganglia and were in close contact
with individual nerve fibers displaying substance P- and calcitonin ge
ne-related peptide-like immunoreactivity. Moreover, serotonin-immunore
active mast cells were innervated with nerve fibers that reacted with
antiserum against vasoactive intestinal polypeptide. At the ultrastruc
tural level, these fibers were almost exclusively identified as unmyel
inated primary sensory afferents. Mast cells contacted these fibers wi
th lamellipodia that wrapped around and enclosed the fibers deeply wit
hin the cell. Close association between mast cells, nerves, and vessel
s was common. Ultrastructural evidence suggests that bidirectional com
munication occurs between nerve fibers and mast cells. These structure
s may participate in axon reflexes that regulate normal vascular and d
etrusor smooth muscle function and cause vasodilation, edema, inflamma
tion, and bladder hyperreactivity. In summary, a close relationship ex
ists between mast cells and peptidergic nerve fibers, including primar
y sensory afferents. Results suggest that bidirectional intel action c
ould occur between nerves and mast cells. (C) 1995 Wiley-Liss, Inc.