P. Hedlund et al., NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum, BR J PHARM, 127(2), 1999, pp. 349-360
1 In the rat corpus cavernosum (CC), the distribution of immunoreactivity f
or neuronal and endothelial NO synthase (nNOS and eNOS), and the pattern of
NOS-immunoreactive (-IR) nerves in relation to some other nerve population
s, were investigated. Cholinergic nerves were specifically immunolabelled w
ith antibodies to the vesicular acetylcholine transporter protein (VAChT).
2 In the smooth muscle septa surrounding the cavernous spaces, and around t
he central and helicine arteries, the numbers of PGP- and tyrosine hydroxyl
ase (TI-I)-IR terminals were large, whereas neuropeptide Y (NPY)-, VAChT-,
nNOS-, and vasoactive intestinal polypeptide (VIP)-IR terminals were found
in few to moderate numbers.
3 Double immunolabelling revealed that VAChT- and nNOS-IR terminals, VAChT-
and VIP-IR terminals, nNOS-IR and VIP-IR terminals, and TH- and NPY-IR ter
minals showed coinciding profiles, and co-existence was verified by confoca
l laser scanning microscopy. TH immunoreactivity was not found in VAChT-, n
NOS-, or VIP-IR nerve fibres or terminals.
4 An isolated strip preparation of the rat CC was developed, and characteri
zed. In this preparation, cumulative addition of NO to noradrenaline (NA)-c
ontracted strips, produced concentration-dependent, rapid, and almost compl
ete relaxations. Electrical field stimulation of endothelin-I-contracted pr
eparations produced frequency-dependent responses: a contractile twitch fol
lowed by a fast relaxant response. After cessation of stimulation, there wa
s a slow relaxant phase. Inhibition of NO synthesis, or blockade of guanyla
te cyclase, abolished the first relaxant phase, whereas the second relaxati
on was unaffected.
5 The results suggest that in the rat CC, nNOS, VAChT-, and VIP-immunoreact
ivities can be found in the same parasympathetic cholinergic neurons. Inhib
itory neurotransmission involves activation of the NO-system, and the relea
se of other, as yet unknown, transmitters.