Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase.
OBJECTIVE
To characterize the distribution of cholinergic nerves in the human corpus cavernosum (CC) and spongiosum (CS) using antibodies to the vesicular acetylcholine transporter (VAChT), and to compare this distribution to those of other transmitters/mediators or transmitter/mediator generating enzymes (heme oxygenases: HO-1 and HO-2; neuronal and endothelial NO synthases: nNOS and eNOS; vasoactive intestinal polypeptide: VIP; and tyrosine hydroxylase: TH), and to investigate NO- and carbon monoxide (CO)-mediated effects.


METHODS
Immunocytochemistry, confocal laser scanning microscopy, radioimmunoassay, and functional in vitro studies.


RESULTS
Along strands of smooth muscle in the CC and CS, rich numbers of VAChT-, nNOS-, VIP-, TH-, and very few HO-1-immunoreactive (-IR) nerve fibers were observed. Immunoreactivities for VAChT and nNOS, VAChT and VIP, and nNOS and VIP, were generally found in the same varicose nerve terminals. TH-IR nerve fibers or terminals did not contain immunoreactivities for VAChT, NOS or VIP. In the endothelium lining penile arteries, immunoreactivities for eNOS, HO-1, and HO-2 were detected. Single endothelial cells, lining the sinusoidal walls of the CC and CS, were found also to contain eNOS and HO-immunoreactivities. Noradrenaline (NA)-contracted preparations of CC and CS were relaxed by NO, CO, carbachol and by electrical stimulation of nerves. Inhibition of NO synthesis abolished electrically- and carbachol-induced relaxation. In NA-activated strips, relaxation induced by exogenously applied NO, but not those by CO, were accompanied by increases in intracellular levels of cyclic GMP.


CONCLUSIONS
VAChT, NOS and VIP are found in the same nerve terminals within the human CC and CS, suggesting that these terminals comprise a distinct population of parasympathetic, cholinergic nerves. Endothelially derived NO and the HO/CO system may have a complementary role in penile erection.
Hedlund
P
P
Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Sweden.
Ny
L
L
Alm
P
P
Andersson
K E
KE
D000109:Acetylcholine / Q000032:analysis; D000328:Adult; D000368:Aged; D002248:Carbon Monoxide / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis; D002799:Cholinergic Fibers / Q000201:enzymology*; D006152:Cyclic GMP / Q000032:analysis; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000201:enzymology / Q000294:innervation; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D009130:Muscle, Smooth / Q000201:enzymology / Q000294:innervation; D009411:Nerve Endings / Q000201:enzymology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis*; D009638:Norepinephrine / Q000494:pharmacology; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000098:blood supply / Q000201:enzymology / Q000294:innervation*; D013566:Sympathomimetics / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D014660:Vasoactive Intestinal Peptide / Q000032:analysis; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; C493459:SLC18A3 protein, human; D013566:Sympathomimetics; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D014446:Tyrosine 3-Monooxygenase; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine