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Localization and Function of Cannabinoid Receptors in the Corpus Cavernosum: Basis for Modulation of Nitric Oxide Synthase Nerve Activity.

Gratzke, Christian; Christ, George J; Stief, Christian G; Andersson, Karl-Erik LU and Hedlund, Petter LU (2010) In European Urology 57. p.342-348
Abstract
BACKGROUND: Anandamide, a proposed endogenous cannabinoid (CB) agonist, has been shown to enhance neurogenic responses in vitro of the rat corpus cavernosal tissue (CC). However, no information is available on the distribution of CB-receptors or effects by anandamide in CC from primates or humans. OBJECTIVE: To characterize the distribution of CB-receptor isoforms in the human and primate CC and to investigate the effects of anandamide on isolated CC preparations. DESIGN, SETTING, AND PARTICIPANTS: CC tissue was excised from the crura penis of six rhesus monkeys and five patients. Expression and distribution CB1 and CB2 receptors were characterized with Western blot analyses and immunohistochemical investigations. The effects of anandamide... (More)
BACKGROUND: Anandamide, a proposed endogenous cannabinoid (CB) agonist, has been shown to enhance neurogenic responses in vitro of the rat corpus cavernosal tissue (CC). However, no information is available on the distribution of CB-receptors or effects by anandamide in CC from primates or humans. OBJECTIVE: To characterize the distribution of CB-receptor isoforms in the human and primate CC and to investigate the effects of anandamide on isolated CC preparations. DESIGN, SETTING, AND PARTICIPANTS: CC tissue was excised from the crura penis of six rhesus monkeys and five patients. Expression and distribution CB1 and CB2 receptors were characterized with Western blot analyses and immunohistochemical investigations. The effects of anandamide on isolated CC preparations were analyzed during pharmacologic and nerve-mediated activation of primate tissue in aerated organ baths. MEASUREMENTS: The expression and localization of CB1 and CB2 receptors in the primate CC and effects of anandamide on nerve-mediated relaxations and pharmacologically evoked contractions. RESULTS AND LIMITATIONS: Western blot experiments revealed CB1 and CB2 receptors at expected band weights. Within and between strands of CC smooth muscle, CB1 and CB2 immunoreactivity (IR) was found in nerve fibers that also expressed IR for nitric oxide synthase (NOS) or transient receptor potential V1 (TRPV1). Neither CB1-IR nor CB2-IR nerves were colocalized with calcitonin-gene-related peptide (CGRP)-containing or tyrosine hydroxylase-containing nerves. No differences were observed between primate and human CC sections. Anandamide (10(-9) to 10(-4) M) had no contractile effects on CC smooth muscle, no relaxant effects on precontracted preparations, and no effect on phenylephrine-induced contractions. However, anandamide (10muM) inhibited electrically evoked smooth-muscle relaxations (34-48%; p</=0.05). CONCLUSIONS: CB1 and CB2 receptors are located on NOS-containing nerves in primate and human CC tissue. In contrast to findings in rats, anandamide antagonized nerve-mediated relaxations of the primate CC, suggesting important species differences for CB-mediated functions. The results also suggest a peripheral mechanism for cannabis-related sexual dysfunction. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Urology
volume
57
pages
342 - 348
publisher
Elsevier
external identifiers
  • wos:000273106400040
  • pmid:19147270
  • scopus:72149121295
ISSN
1873-7560
DOI
10.1016/j.eururo.2008.12.024
language
English
LU publication?
yes
id
db744425-0eb4-4fe2-b0f8-5626f95e9f14 (old id 1289663)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19147270?dopt=Abstract
date added to LUP
2009-02-03 11:30:03
date last changed
2017-01-01 07:42:13
@article{db744425-0eb4-4fe2-b0f8-5626f95e9f14,
  abstract     = {BACKGROUND: Anandamide, a proposed endogenous cannabinoid (CB) agonist, has been shown to enhance neurogenic responses in vitro of the rat corpus cavernosal tissue (CC). However, no information is available on the distribution of CB-receptors or effects by anandamide in CC from primates or humans. OBJECTIVE: To characterize the distribution of CB-receptor isoforms in the human and primate CC and to investigate the effects of anandamide on isolated CC preparations. DESIGN, SETTING, AND PARTICIPANTS: CC tissue was excised from the crura penis of six rhesus monkeys and five patients. Expression and distribution CB1 and CB2 receptors were characterized with Western blot analyses and immunohistochemical investigations. The effects of anandamide on isolated CC preparations were analyzed during pharmacologic and nerve-mediated activation of primate tissue in aerated organ baths. MEASUREMENTS: The expression and localization of CB1 and CB2 receptors in the primate CC and effects of anandamide on nerve-mediated relaxations and pharmacologically evoked contractions. RESULTS AND LIMITATIONS: Western blot experiments revealed CB1 and CB2 receptors at expected band weights. Within and between strands of CC smooth muscle, CB1 and CB2 immunoreactivity (IR) was found in nerve fibers that also expressed IR for nitric oxide synthase (NOS) or transient receptor potential V1 (TRPV1). Neither CB1-IR nor CB2-IR nerves were colocalized with calcitonin-gene-related peptide (CGRP)-containing or tyrosine hydroxylase-containing nerves. No differences were observed between primate and human CC sections. Anandamide (10(-9) to 10(-4) M) had no contractile effects on CC smooth muscle, no relaxant effects on precontracted preparations, and no effect on phenylephrine-induced contractions. However, anandamide (10muM) inhibited electrically evoked smooth-muscle relaxations (34-48%; p&lt;/=0.05). CONCLUSIONS: CB1 and CB2 receptors are located on NOS-containing nerves in primate and human CC tissue. In contrast to findings in rats, anandamide antagonized nerve-mediated relaxations of the primate CC, suggesting important species differences for CB-mediated functions. The results also suggest a peripheral mechanism for cannabis-related sexual dysfunction.},
  author       = {Gratzke, Christian and Christ, George J and Stief, Christian G and Andersson, Karl-Erik and Hedlund, Petter},
  issn         = {1873-7560},
  language     = {eng},
  pages        = {342--348},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Localization and Function of Cannabinoid Receptors in the Corpus Cavernosum: Basis for Modulation of Nitric Oxide Synthase Nerve Activity.},
  url          = {http://dx.doi.org/10.1016/j.eururo.2008.12.024},
  volume       = {57},
  year         = {2010},
}