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Localization and function of cannabinoid receptors in the corpus cavernosum: basis for modulation of nitric oxide synthase nerve activity.

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 of 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

journal_name

Eur Urol

journal_title

European urology

authors

Gratzke C,Christ GJ,Stief CG,Andersson KE,Hedlund P

doi

10.1016/j.eururo.2008.12.024

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

342-8

issue

eissn

0302-2838

issn

1873-7560

pii

S0302-2838(08)01499-1

journal_volume

pub_type

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Localization and function of cannabinoid receptors in the corpus cavernosum: basis for modulation of nitric oxide synthase nerve activity.