Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase

Petter Hedlund, Lars Ny, Per Alm, Karl Erik Andersson

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Materials and 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.

Original languageEnglish
Pages (from-to)868-875
Number of pages8
JournalJournal of Urology
Volume164
Issue number3 I
Publication statusPublished - Sep 2000

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Vesicular Acetylcholine Transport Proteins
Heme Oxygenase (Decyclizing)
Nitric Oxide Synthase
Cholinergic Agents
Carbon Monoxide
Carbachol
Nerve Fibers
Norepinephrine
Penile Erection
Heme Oxygenase-1
Vasoactive Intestinal Peptide
Cyclic GMP
Tyrosine 3-Monooxygenase
Confocal Microscopy
Electric Stimulation
Endothelium
Radioimmunoassay
Smooth Muscle
Endothelial Cells
Arteries

Keywords

  • Co-localization
  • Confocal microscopy
  • Innervation
  • Penile erection

ASJC Scopus subject areas

  • Urology

Cite this

Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. / Hedlund, Petter; Ny, Lars; Alm, Per; Andersson, Karl Erik.

In: Journal of Urology, Vol. 164, No. 3 I, 09.2000, p. 868-875.

Research output: Contribution to journalArticle

Hedlund, P, Ny, L, Alm, P & Andersson, KE 2000, 'Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase', Journal of Urology, vol. 164, no. 3 I, pp. 868-875.
Hedlund, Petter ; Ny, Lars ; Alm, Per ; Andersson, Karl Erik. / Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. In: Journal of Urology. 2000 ; Vol. 164, No. 3 I. pp. 868-875.
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T1 - Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase

AU - Hedlund, Petter

AU - Ny, Lars

AU - Alm, Per

AU - Andersson, Karl Erik

PY - 2000/9

Y1 - 2000/9

N2 - Purpose: 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. Materials and 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.

AB - Purpose: 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. Materials and 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.

KW - Co-localization

KW - Confocal microscopy

KW - Innervation

KW - Penile erection

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